What Is A Translation In Biology

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  • Protein synthesis is usually broken down into 2 parts in conventional biology: Transcription and translation.(More...)

POSSIBLY USEFUL

  • Translation is the process by which a protein is synthesized by the assembly of amino acids into polypeptide chains according to the "code" of the mRNA sequence.(More...)

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What Is A Translation In Biology
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KEY TOPICS

Protein synthesis is usually broken down into 2 parts in conventional biology: Transcription and translation. [1] Translation, the second part of the central dogma of molecular biology, describes how the genetic code is used to make amino acid chains. [2]

With Reverso you can find the English translation, definition or synonym for biology and thousands of other words. [3]

The process of decoding the instructions in DNA to make RNA, which in turn is decoded to make a specific protein is known as the central dogma of molecular biology. [4] In biology a or genetics course, some classes may want you to take an mRNA sequence and figure out what sequence of tRNAs, and hence amino acids, it codes for. [5] This site archives newsletters dedicated to my open biology courses taught from Georgia State University in Atlanta, GA. The course focuses on the principles of cell and molecular biology. [6]

POSSIBLY USEFUL

Translation is the process by which a protein is synthesized by the assembly of amino acids into polypeptide chains according to the "code" of the mRNA sequence. [7] Translation is a process by which the genetic code contained within an mRNA molecule is decoded to produce the specific sequence of amino acids in a polypeptide chain. [8]

Each tRNA anticodon can base pair with one of the mRNA codons and add an amino acid or terminate translation, according to the genetic code. [9] Translation begins when a ribosome binds to an mRNA strand and an initiator tRNA. The initiator tRNA delivers an amino acid called 'methionine' directly to the P site and keeps the A site open for the second tRNA molecule to bind to. [10] Translation requires the input of an mRNA template, ribosomes, tRNAs, and various enzymatic factors. [9] Moderately stable hairpins upstream of an AUG codon and close to the 5? end of a transcript are known to suppress translation efficiency, presumably by impacting the ability of ribosomes to load onto the mRNA. Mutation and deletion experiments that reduce hairpin stability generally result in an increase in the amount of the encoded protein. [7] The formation of secondary structure(s) involving the 5? leader sequence of the mRNA can limit or altogether suppress translation and this mode of gene regulation has been observed in both plant and animal models, presumably to prevent the over-expression of a specific protein. [7] Because eukaryotic mRNAs acquire a circular conformation, bringing the 3? end of the transcript close to the 5? cap and the 5?-UTR, it appears that either the association of proteins, the formation of secondary structures within the 3?-UTR, or perhaps both, influence overall translation efficiency. [7] Translation is the process where the information carried in mRNA molecules is used to create proteins. [10] Genetic translation refers to the process whereby messenger RNA (mRNA) serves as a template for ribosome-mediated protein synthesis. [7] The process of translation, or protein synthesis, involves the decoding of an mRNA message into a polypeptide product. [9] In a nutshell, DNA translation can be defined as the process that "translates" information contained in the nucleic acids (DNA and RNA) to facilitate polypeptide or protein synthesis. [11] During translation, the RNA molecule created in the transcription process delivers information from the DNA to the protein building machines. [10] Transcription and translation are the two processes that convert a sequence of nucleotides from DNA into a sequence of amino acids to build the desired protein. [10] Transcription and translation take the information in DNA and use it to produce proteins. [10]

The antiviral effect of IFN would equally affect the translation of both viral mRNA and cellular mRNA. Nonetheless, the host cells are less vulnerable, since host proteins have already accumulated to some extent. [7] During translation mRNA nucleotide bases are read as three base codons, each of which codes for a particular amino acid. [8] Scanning begins at the 5? capped end of the mRNA and halts at the first initiator codon, usually AUG, where translation begins. [7] In the leaders for many eukaryotic mRNAs, the first AUG initiates translation of an upstream open reading frame (uORF) which is typically short. [7]

Translation ends when a stop codon on the mRNA strand reaches the A site in the ribosome. [10] The key components required for translation are mRNA, ribosomes, tRNA and aminoacyl-tRNA synthetases. [8] The mRNAs decoded in translation are obtained from a process known as transcription. [11] In addition to the mRNA template, many molecules and macromolecules contribute to the process of translation. [9] Translation is initiated by the binding of a messenger RNA (mRNA) to the ribosomal small subunit. [7] Translation produces polypeptides as a result of decoding of mRNA. [11] In one study, Kunes and colleagues found that the mRNA encoding CaMKII ? was present in dendrites of Drosophila neurons and noted that the 3?UTR contained two putative miRNA binding sites, indicating that binding of miRNAs might function to repress translation. [7] As specific mRNAs may contain multiple regulatory elements, the control of translation may place mRNAs in a unique position to act as coincidence detectors, integrating several stimuli in order to regulate protein synthesis. [7] Protein synthesis is a vital process that takes place in the ribosomes of cells of living beings and translation forms an important part of it. [11] Certain uORFs enhance downstream translation, probably because the uORF sequence facilitates reinitiation of translation at downstream AUG codons. uORFs which diminish downstream translation are believed to interfere with ribosome scanning beyond the uORF. Current evidence from studies of a cytomegalovirus uORF-encoded peptide indicate that the short peptide prevents ribosome release from the uORF termination codon. [7] Several features of the leader sequence can dramatically decrease translation of the main (downstream) coding sequence: examples include a region of secondary structure proximal to the 5? cap site or a 5? proximal AUG codon lacking a following an open reading frame. [7]

During translation, the information of the strand of RNA is "translated? from RNA language into polypeptide language i.e. the sequence of nucleotides is translated into a sequence of amino acids. [10]

Translation of the functional protein, therefore, requires translation of the uORF, followed by scanning of the ribosome to the next AUG and reinitiation of translation. [7] Peptidyl transfer is catalyzed by the rRNA of the large subunit without direct assistance of ribosomal proteins or translation factors. [7] The production of proteins is completed through two processes: transcription and translation. [10] Translation is a series of variegated biochemical events acting concertedly to sustain the production of proteins. [7]

Of these 61, one codon (AUG) also known as the "start codon" encodes the initiation of translation. [9] There are also specific codons that signal the start and the end of translation. [8] Activation The process of translation starts with 'activation', which actually is not a step, but the starting point of the process. [11] It is the first step in the process and is known as translation. [11] Translation is of fundamental importance as a phase of gene expression and an energetically expensive process whose regulation is critical for cellular energy economy. [7] In this article we will look at the stages of translation and compare the process in prokaryotes and eukaryotes. [8] Guanosine-5'-triphosphate (GTP) provides energy for the process of translation. [11]

Cap-independent translation of IRES-containing poliovirus mRNA is still to occur. [7] MRNA translation has emerged as a target for anticancer therapy. [7] Given the large number of mRNAs that have been identified as being dendritically and/or axonally localized, this is not surprising, since one would expect that distinct stimuli would activate the translation of distinct mRNAs via distinct signaling pathways. [7] No further modifications are required for the mRNA molecule and it is possible for translation to begin immediately. [10] The remaining sections are spliced together and the final mRNA strand is ready for translation. [10]

Translation is traditionally divided into three steps: initiation, elongation, and termination. [7] In some studies, stimulus-induced translation of localized mRNAs has been shown to recruit rapamycin-dependent translational regulation, a mechanism involving regulation of translational initiation via the terminal oligopyrimidine tracts within the 5?UTR regions of specific mRNAs. [7] Edelman and colleagues, working in vertebrate neurons, and Sossin and colleagues, working in invertebrate neurons, have proposed that translation of mRNAs using internal ribosomal entry sites provides an additional mechanism for specifically regulating the translation of several localized mRNAs at synapses. [7] The translation of localized mRNAs appears to be regulated by multiple mechanisms. [7] This translation regulatory mechanism appears to be widespread in animals (Allard et al., 2005; Wax et al., 2005), in plants (Browning, 1996), and among plant viruses (Guo et al., 2001). [7]

Increased expression or differential phosphorylation of these initiation factors leads to changes in cellular translation rates, which can result in drastic changes in growth, proliferation, differentiation, and survival. [7] Translation results when an engaged ribosome is unencumbered as it moves along a transcript until it reaches a stop codon. [7] Translation in prokaryotes is similar apart from the presence of simpler ribosomes (70s type). [8] IRESs can initiate translation by promoting ribosome binding within a transcript and initiate translation without a start codon. [7] The small and large subunits of the ribosome dissociate ready for the next round of translation. [8]

In eukaryotic cells, transcription of a DNA strand must be complete before translation can begin. [10] Translation Suppression : Notably, cellular translation function is severely impaired in poliovirus infected cells. [7]

The tRNA that has formed a covalent bond with methionine during the activation phase of translation becomes a part of the complex structure called 'ribosomal complex'. [11] Translation in eukaryotes is typically initiated by the scanning of a 40S ribosomal preinitiation complex. [7] Translation can begin in bacteria while transcription is still occurring. [10] Transcription and translation also take place simultaneously in prokaryotes. [8]

More than 10 factors participate in eubacterial translation, whereas a considerably larger number participate in eukaryal translation. [7] Poliovirus subverts the host translation machinery for viral protein synthesis. [7] Increased translation as a result of overexpression of eIF4E, or inappropriate activation of mTOR signaling to the 4E-BPs is implicated in a variety of human cancers. [7] Stimulus-induced translation of localized mRNAs has also been shown to be mediated by regulation of cytoplasmic polyadenylation. [7] For translation to start the start codon 5?AUG must be recognised. [8]

Interestingly, mRNAs containing these tracts include many of the ribosomal proteins as well as translation initiation and elongation factors. [7] For translation initiation, the small ribosomal subunit must bind to the mRNA to form, along with initiation factors, an initiation complex. [7] Translation initiation is a highly ordered process that is regulated primarily by phosphorylation of initiation factors, in particular those that are involved in 5? mRNA cap recognition and eIF4F complex formation. [7] Which other components of the translation initiation machinery are required for axonal mRNA translation and how the process is spatiotemporally regulated are currently unknown. [7] Recent reports suggest that the 3? UTR (the trailer sequence of an mRNA), may have a profound role regulating translation initiation. [7] Therefore, eukaryotic cells have evolved intricate mechanisms to regulate mRNA translation initiation. [7] The process of translation occurs in the cytoplasm of a cell and can be divided into three distinct phases: translation initiation, polypeptide chain elongation, and chain termination. [7]

If any of the termination codon enters the 'A' site of the ribosome, the translation process stops. [11] The protein formed as a result of this whole process, is released from the ribosome and finally the translation process ends. [11] The translation process takes place in the cell cytoplasm, specifically where the cell organelle, ribosome is present. [11]

The process of translation occurs on the ribosome in the cytoplasm or in the cellular organelles, mitochondria and chloroplasts. [7] Despite the recent success of anticancer therapies designed to inhibit translation, either by targeting eIF4E directly or suppressing mTOR, it is imperative that we continue to study the mechanisms of translational control in order to fully understand the process of translation initiation and its role in human disease. [7] Future studies focusing on the role of eIF4E phosphorylation in translation initiation and its potential involvement in malignant transformation are required. [7]

An IRES presumably functions in an analogous manner to a bacterial ribosome binding site in allowing translation initiation by directly serving as a ribosome-binding target. [7] Interestingly, a -19 kcal/mol hairpin 14 nts downstream from an AUG codon can actually enhance translation initiation ( Kozak, 1990 ), possibly because the hairpin causes strategic pausing of the ribosome directly over the start codon, thereby enhancing translation initiation. [7] Translation initiation efficiency at any particular AUG is affected by the context of the leader sequence flanking the AUG codon; a preinitiation complex may ignore an AUG codon located in a region of poor context. [7]

Termination It is the final phase of the translation process. [11]

In translation, mRNA along with tRNA and ribosomes work together to produce a protein. [12] Therefore, in translation, Codons on mRNA are being translated into a sequence of amino acids that forms a polypeptide chain. [1] How is RNA translated into a series of amino acids? Learn the language of the genetic code, explore a codon dictionary, and discover some basics of genetics in this lesson on translation. [2] In vitro RNA transcription reactions are generally used for two distinct purposes: the synthesis of labeled probes, and the synthesis of large amounts of unlabeled RNA. Capped RNA synthesized in transcription reactions is also used for microinjection, in vitro translation, and transfection. [13] In vitro transcription and in vitro translation replicate the processes of RNA and protein synthesis outside of the cellular environment. [13]

We'll use a simple analogy to explore the roles of transcription and translation in building protein from the DNA code. [2] An overview of the two stages of protein production: Transcription and Translation. [4]

Ribosomes play a major role in the process of genetic translation. [2] Once messenger RNA has been modified and is ready for translation, it binds to a specific site on a ribosome. [12] Transfer RNA plays a huge role in protein synthesis and translation. [12] Protein synthesis is accomplished through a process called translation. [12]

During translation, a small ribosomal subunit attaches to a mRNA molecule. [12] Once all modifications are complete, mRNA is ready for translation. [12] Once it has transcribed the DNA, mRNA binds to a ribosome, an organelle in the cell where translation occurs. [1]

The Transcription and Translation Process chapter of this course is designed to help you plan and teach the stages of protein synthesis in your classroom. [2] Below is a sample breakdown of the Transcription and Translation Process chapter into a 5-day school week. [2]

Transcription and translation are processes a cell uses to make all proteins the body needs to function from information stored in the sequence of bases in DNA. The four bases (C, A, T/U, and G in the figure) are the building blocks of DNA and RNA. During transcription, a piece of DNA that codes for a specific gene is copied into messenger RNA (mRNA) in the nucleus of the cell. [14] Our understanding of the mechanism by which the ribosome is reprogrammed at multiple sites in the same RNA during translation to incorporate Sec has been limited by the inability to quantify the formation of unstable termination products ( 31 ) relative to the various full-length and near full-length SELENOP proteins in vivo. [15] During translation, selenoprotein transcripts recruit the SECIS RNA binding protein (SECISBP2) ( 13, 14 ) and a specialized Sec elongation factor (eEFSec) that delivers Sec-tRNA Sec to the ribosome ( 15 - 17 ). [15]

Translation is accomplished by the ribosome, which links amino acids in an order specified by messenger RNA (mRNA), using transfer RNA (tRNA) molecules to carry amino acids and to read the mRNA three nucleotides at a time. [16] We further propose that secondary and tertiary interactions within and possibly between larger regions of the mRNA coding sequence may be involved in coordinating UGA redefinition, rates of translation elongation, and the selective use of SECIS elements by the ribosome during translation of Selenop. [15] Ribosome profiling of mouse livers carrying a deletion of either SECIS1 or SECIS2 indicates that the loss of SECIS2 primarily affects Sec incorporation at the first UGA, while the loss of SECIS1 affects processive Sec incorporation during translation of the UGA-rich region near the 3? end of the SELENOP coding sequence (D). [15] ISL, Initiator stem loop; SP, signal peptide; the position of the first UGA in Selenop is indicated; Rluc, Renilla luciferase; SECIS1 and SECIS2 are located just downstream of Rluc. ( B ) In vitro transcription and translation of the indicated reporter constructs in the presence or absence of SECISBP2. 35-S methionine labelled proteins were electrophoresed and visualized by phosphor image analysis. [15] To determine if changes in SELENOP synthesis might alter available selenium pools and affect translation of other selenoproteins, RPFs mapping to regions upstream (CDS5) or downstream (CDS3) of UGA Sec codons were normalized for gene length and total mapped sequence reads in each sample (RPFKMs, RPF reads per kilobase per million mapped reads). [15] The products of Selenop translation consist of a shortened N-terminal isoform having the first Sec residue in a thioredoxin-like motif with presumed peroxidase activity ( 24 ) terminating at the second Sec residue, as well as longer isoforms that terminate at Sec positions within the C-terminal Sec-rich domain ( 25, 26 ) or at the natural termination codon. [15] A The codon AUG both codes for methionine and serves as an initiation site: the first AUG in an mRNA's coding region is where translation into protein begins. [16] "Generation of protein isoform diversity by alternative initiation of translation at non-AUG codons". [16]

A striking example of UGA redefinition occurs during translation of the mRNA coding for the selenium transport protein, selenoprotein P (SELENOP), which in vertebrates may contain up to 22 in-frame UGA codons. [15] Despite the aforementioned inefficiency in Sec incorporation, the production of long SELENOP isoforms demands that Sec incorporation at some UGA-Sec codons must occur with high efficiency while production of the short isoform requires some UGA codons to terminate translation suggesting that unique mechanisms may be involved in translation of the Selenop mRNA. [15] Studies of Selenop translation using a SECISBP2 supplemented in vitro translation system indicated that after incorporation of selenocysteine at a first UGA codon, incorporation at downstream UGA codons occurs with much higher efficiency ( 28, 29 ). [15]

As shown in Figure 3B, in vitro translation of capped native huSELENOP mRNA in the presence of yielded a distinct ?47kDa protein (note this is 3 kDa larger than the predicted molecular weight of 44 kDa). [15] During translation, proteins are made using the information stored in the mRNA sequence. [14] We have used a fully reconstituted in vitro translation system to probe the NMD proteins for interaction with the termination apparatus. [17] Translation of Luc10UGA produced protein that was visualized as a weak and diffuse band at ?44kDa that likely represents full length protein as well as early termination products at one or more of the C-terminal UGA codons. [15] Biosynthesis of selenoproteins is unique in that the incorporation of Sec occurs during translation in response to an in-frame UGA codon, which in standard decoding specifies termination. [15] The process of UGA redefinition and Sec incorporation has consistently been shown to be inefficient due, at least in part, to the requirement for specialized Sec insertion factors to recruit the Sec-tRNA Sec in a process that competes with termination of translation. [15] Nearby sequences such as the Shine-Dalgarno sequence in E. coli and initiation factors are also required to start translation. [16] We thank Elena Alkalaeva for providing Met?tRNA and the plasmids for initiation factors used for in vitro translation, Alain Miller (Calbiotech S.A., Mons, Belgium) for providing HeLa cytoplasmic extracts, Jan Medenbach for the gift of SXL, and Dmytro Dziuba for the gift of IRP1. [17] In vitro translations were conducted in the presence of L- -Methionine using the TnT T7 Quick Coupled Transcription /Translation System (Promega) in the presence or absence of exogenous SECISBP2 protein. [15] These mutations usually result in a completely different translation from the original, and likely cause a stop codon to be read, which truncates the protein. [16] These results reveal a number of RNA elements acting to control translation, RNA stability, SELENOP secretion and codon redefinition during SELENOP synthesis. [15] The core concept of translation is the connecting of a codon to an amino acid, which is accomplished with the Transfer RNAs. [6] To create a functional protein, translation must end with the appropriate amino acid. [6] If translation stops to soon, the protein will be too short and may not bend (configure) correctly. [6]

To examine the effect of deleting SECIS1 and SECIS2 on translation of Selenop, the A-site positions for each RPF were determined along the length of the mRNA, summed at each position and normalized against the total number of mapped RPF reads (reads per million mapped reads) and Selenop mRNA abundance (reads per million mapped reads). [15] Summary Figure of SELENOP structures and regions and their effects on SELENOP synthesis. ( A ) Indicates the activity of ISL on overall translation. ( B ) Illustrates that SRE1 structure affects UGA redefinition at the first UGA. ( C ) The activity of SECIS2 is sensitive to selenium levels. [15] We observed that mutations of the ISL that overlap the signal peptide sequence of Selenop significantly reduced translation efficiency and that this effect was independent of the presence of the first UGA or the inclusion of SECISBP2. [15]

Small variants such as translation of the codon UGA as tryptophan in Mycoplasma species, and translation of CUG as a serine rather than leucine in yeasts of the "CTG clade" (such as Candida albicans ). [16] The frequency of codons, also known as codon usage bias, can vary from species to species with functional implications for the control of translation. [16] Daily Newsletter March 29, 2012 Today's Topic: Translation The core concept of translation is the connecting of a codon to an a. [6]

For the experiment described in Fig 1 E, 3 pmol of UPF1 was incubated in ATP'supplemented translation buffer either alone or in the presence of equal amounts of UPF2L and/or UPF3B and with or without 50 fmol SMG1?8?9 as indicated for 30 min at 37C. After the addition of pre?TCs, the mixture was incubated for 10 min at 37C. The termination reaction was initiated by the addition of eRF1 and eRF3a and allowed to proceed for 5 min. [17] Under in vitro translation conditions at pH 7.5 and 37C (Fig EV1 E), neither UPF2L (lane 5) nor UPF3B (lane 6) had a significant effect on the ATPase function of UPF1. [17] Briefly, 1.5 pmol UPF1 either alone or in presence of 3 pmol UPF2L and/or 3 pmol UPF3B was mixed with 4 ?l 5MES buffer (250 mM MES pH 6.5, 250 mM KOAc, 25 mM Mg(OAc) 2, 10 mM DTT, 0.5 mg/ml BSA) or 5translation buffer (100 mM Tris pH 7.5, 500 mM KCl, 12.5 mM MgCl 2, 10 mM DTT, 1.25 mM spermidine), 2 ?l Poly(U) RNA (Sigma, 2 mg/ml in H 2 O) and H 2 O to a final volume of 16 ?l. [17] Thin layer chromatography (TLC) analysis of the ATPase activity of UPF1 variants in the absence or presence of UPF2L and/or UPF3B at 30C in MES buffer (pH 6.5, lanes 1-7) or translation buffer (pH 7.5, lanes 8-13), respectively. 1.5 ?l of the samples was spotted on the TLC plates, and the residual 18.5 ?l was analysed on SDS-PAGE gels for loading control (lower panels). [17]

This conclusion is indirectly supported by the finding that directing UPF3B close to the 3? end of the ORF stimulates translation of a reporter RNA in vivo (Kunz et al, 2006 ). [17] In order to investigate the effects of the ISL on translation of the Selenop RNA, we designed reporter constructs for translation in vitro as follows. [15] We repeated in vitro translation in the presence of Cys of the cysteine versions huCysSELENOP and Luc10UGC respectively (Figure 3B, right), which demonstrates that the difference in migration of huSELENOP and Luc10UGA translated products is intrinsic and not due to premature termination. [15] UPF3B's potential role in eRF3a recruitment or its inability to recruit eRF3a?N could thus be bypassed by eRF1 and, therefore, cannot be mirrored by the in vitro translation system. [17] In vitro translation assay was performed as described earlier ( 29 ). [15] Translation is modulated by the Mg 2+ concentration both in vivo and in vitro. [17] We are much obliged to Tatyana Pestova for generously introducing KK to the reconstituted in vitro translation system and for providing the MVHC?STOP plasmid. [17]

During translation, StopGo sequences located at the 3? end of Rluc and the 5? end of Fluc induce peptide cleavage and release of each reporter enzyme respectively. ( B ) Reporter constructs containing SECIS1 were transfected into HEK293 cells and % Recoding is expressed as the ratio of firefly to Renilla luciferase normalized to a construct lacking the UGA codon. [15] The genetic code is so well-structured for hydropathy that a mathematical analysis ( Singular Value Decomposition ) of 12 variables (4 nucleotides x 3 positions) yields a remarkable correlation (C 0.95) for predicting the hydropathy of the encoded amino acid directly from the triplet nucleotide sequence, without translation. [16]

We conclude that SECIS1 is more important for translation of UGA codons downstream of the first UGA, compared to the first UGA. [15] Aliquots containing 0.01 pmol of ?methionine?containing pre?TCs were incubated for 10 min at 37C with 0.3 pmol BSA or UPF3B in translation buffer E supplemented with 1 mM ATP and 0.5 mM GTP. The peptide release reaction was started by addition of termination?rate limiting amounts eRF1 and eRF3a. [17] The same analysis was conducted for hepatic translation of Selenop in the SECIS2 deletion mutant and matched wild type controls (Figure 6D - F ). [15] A reading frame is defined by the initial triplet of nucleotides from which translation starts. [16] Remember that a tRNA essentially acts as an adapter in translation. [5] As an example for addressing stop codon evolution, it has been suggested that the stop codons are such that they are most likely to terminate translation early in the case of a frame shift error. [16] Translation starts with a chain-initiation codon or start codon. [16] To test whether UPF proteins affect the efficiency of translation termination, equal amounts of pre?TCs that had been assembled on MVHC?STOP mRNA and purified by SDG centrifugation were incubated with UPF1, UPF2L, UPF3B or combinations of these proteins as indicated (Fig 1 B, lanes 3-9). [17] All prevailing models from yeast to man ascribe a critical role to UPF1 not only in the mRNA degradation phase, but already in the translation termination phase of NMD. These hypotheses are founded on the interaction of UPF1 with eRF1 and eRF3a, which were identified in co?IP experiments (Wang et al, 2001 ; Ivanov et al, 2008 ; Singh et al, 2008 ) (Fig 2 ). [17] Our discovery that UPF1 can directly interact with UPF3B contributes to the understanding of the UPF2?independent NMD branch, since UPF2 was assumed to bridge between UPF1 and UPF3B. However, if a major role of UPF3B in NMD is confined to translation termination, it remains to be investigated how ribosomes stalled at a PTC are recognized in the UPF3B?independent branch. [17] We identified UPF1 and ribosomes as new interaction partners of UPF3B. These previously unknown functions of UPF3B during the early and late phases of translation termination suggest that UPF3B is involved in the crosstalk between the NMD machinery and the PTC?bound ribosome, a central mechanistic step of RNA surveillance. [17]

The effect of UPF3B in delaying translation termination may also involve direct binding to the ribosome, thus interfering with efficient stop codon recognition by the release factors. [17] Unexpectedly, UPF1 plays no discernible functional role in this context, suggesting that it acts downstream to promote NMD. Importantly, UPF3B delays translation termination when release factors are limiting and dissolves post?termination complexes after peptidyl?tRNA hydrolysis. [17] In agreement with current models, we hypothesized that in such a system the central NMD factor UPF1 interacts with the eRFs and possibly the ribosome (Min et al, 2013 ), thereby delaying translation termination. [17] Although the necessity of an interaction between the UPF proteins and the translation termination apparatus is generally accepted, the sequence and timing of NMD factor recruitment to the termination site have not been addressed experimentally. [17]

The factors described here induce the native SELENOP mRNA to adopt distinct structures that act to control translation initiation and codon-specific UGA redefinition efficiencies such that SELENOP synthesis is optimized for cellular needs and selenium delivery throughout the body. [15] We conclude that, when expressed in partially purified reticulocyte translation reactions, the ISL acts to enhance translation initiation on Selenop mRNA and that it does not have an effect on redefinition of the first UGA. [15]

Previous observations that several selenoproteins have hypermethylated cap structures at their 5? end ( 41 ) and that initiation from an internal ribosome entry site results in significant reductions in Sec incorporation efficiency ( 42 ) suggest that events occurring during translation initiation may be relevant to UGA redefinition events that occur downstream. [15] Using reporter assays, we find a highly conserved ISL stem loop structure overlapping the signal peptide region that can facilitate translation initiation (A), a SRE1 structure downstream of the first UGA that acts to stimulate Sec incorporation (B), and further we find that while both SECIS1 and SECIS2 can support inefficient Sec incorporation at the first UGA (green dotted lines), the activity of SECIS2 is sensitive to selenium levels (C). [15]

The data support a novel RNA structure near the start codon that impacts translation initiation, structures located adjacent to UGA codons, additional coding sequence regions necessary for efficient production of full-length SELENOP, and distinct roles for SECIS1 and SECIS2 at UGA codons. [15]

Nonsense?Mediated Decay (NMD)?factor UPF3B plays a dual role in early and late translation termination, suggesting a role in coordinating the crosstalk between the NMD machinery and the PTC?bound ribosome. [17] UPF3B delays translation termination in vitro Scheme of the MVHC?STOP mRNA. [17] NMD?factor UPF3B interferes with translation termination in vitro when release factors are limiting. [17] We analyse whether UPF1 alone or together with UPF2 and/or UPF3B affects the efficiency of mammalian translation termination in vitro. [17] We explored whether in vitro phosphorylation of UPF1 affects translation termination. [17] These findings indicate that when the eRFs are limiting, neither UPF1 nor UPF2L has a direct effect on translation termination in vitro. [17] Surprisingly, we find that neither UPF1 per se nor its biochemical functions such as ATP binding, ATP-hydrolysis or its phosphorylation play a discernible role in early or late phases of translation termination. [17] Independent of its functions in ATP binding or ATP hydrolysis or of its phosphorylation status, UPF1 has no impact on translation termination even when eRFs are present at saturating concentrations. [17]

Yeast Upf1p has recently been implicated in translation termination and ribosome release at PTCs (Serdar et al, 2016 ), an activity that required Upf1p's ATPase function as well as Upf2p and Upf3p. [17] Model for early and late UPF3B function in translation termination During termination at a PTC ribosome?bound UPF3B interacts with the eRF1/eRF3a?GTP complex impeding efficient stop codon recognition. [17] These findings suggest that the effect of UPF3B on translation termination can be fully or partially mediated by a direct interaction of UPF3B with either eRF3a or the eRF1?eRF3a complex. [17]

We discovered that UPF3B (i) interacts with the release factors, (ii) delays translation termination and (iii) dissociates post?termination ribosomal complexes that are devoid of the nascent peptide. [17] When release factors are limiting and translation termination is inefficient, UPF3B further delays termination and inhibits peptide release. [17]

It has not been possible to experimentally address the hypothetical functions of NMD factors in translation termination in cells and organisms, because no adequate in vivo termination assay is available to date. [17] We tested the functional interactions of key NMD factors in vitro using a fully reconstituted translation termination system that has been demonstrated to faithfully mirror all phases of eukaryotic translation (Alkalaeva et al, 2006 ; Pisarev et al, 2007b ; Pisareva et al, 2008 ). [17]

Conceptually, NMD can be divided into a translation termination phase and an mRNA degradation phase. [17] The mRNA then carries the genetic information from the DNA to the cytoplasm, where translation occurs. [14] In prokaryotes, translation occurs as soon as the mRNA comes off the DNA template. [18]

In eukaryotes, transcription takes place in the nucleus, travels through protein membranes and reaches the cytoplasm where translation occurs. [18] It is unclear whether these manipulations disturb or reflect direct interactions of UPF proteins with the translation termination machinery. [17] The mechanism by which translation termination at a PTC is distinguished from termination at a normal termination codon (NTC) is still poorly understood. [17] How translation termination at a premature termination codon differs from termination at a NTC has long been a matter of debate. [17]

Ribosome recycling after proper or faulty translation termination is crucial for the protein synthesis machinery to avoid sequestration of essential components of the translation apparatus. [17] Translation termination, whether regular or aberrant, needs to recycle ribosomes to avoid deleterious consequences for the translation apparatus (Graille & Seraphin, 2012 ; Lykke?Andersen & Bennett, 2014 ). [17]

Unexpectedly, we discover that UPF3B exerts the bifunctional influence on translation termination that has hitherto been attributed to UPF1. [17] Addition of UPF2L abolished the effect of UPF3B on translation termination (lane 7, 8) confirming that the termination delay is specifically caused by UPF3B and indicating that binding to UPF2L may prevent UPF3B from interfering with the termination reaction. [17] We tested truncated versions of UPF3B for their capacity to delay translation termination. [17]

During translation termination, eRF1 in complex with eRF3a binds to the stop codon (Brown et al, 2015 ) inducing conformational rearrangements. [17] To shed light on these critical aspects of translation termination in an NMD context, we adopted an approach that combines a fully reconstituted in vitro translation termination system with in vitro and in vivo interaction studies to decipher the UPF?eRF interactome in translation termination. [17] Neither eIF4B (RNA? and ribosome?binding), nor IRP1 (RNA?binding), or SXL (RNA?binding, pI 9.5) had an influence on in vitro translation termination (Fig EV2 B). [17] In vitro translation termination was performed essentially as described (Alkalaeva et al, 2006 ). [17]

Based on co?immunoprecipitation (co?IP) experiments, human UPF1 has been suggested to interact with both eRF1 and eRF3a and thereby physically link the NMD apparatus with translation termination (Kashima et al, 2006 ; Ivanov et al, 2008 ; Singh et al, 2008 ). [17] The N?terminus of eRF3a is not required for the function of eRF3a in translation termination (Ter?Avanesyan et al, 1993 ). [17]

These results are consistent with the stem loop increasing the overall rate of translation initiation in reticulocyte lysate translation reactions. [15]

Our redox proteomic results revealed that oxidative stress induced by H 2 O 2 treatment modulates the oxidation of ribosomal subunits and further proteins involved in translation (Supplementary Fig.   3b and c and Table  1 ). [19] The response to attenuate translation upon H 2 O 2 treatment was decreased in the cells lacking these ribosomal proteins (Figs.   6d, e ). [19] Proteins involved in translation comprise H 2 O 2 -sensitive thiols ( P- value < 0.05, n   3; difference in % oxidation ≥ 7) within CX 2 C-X (9–47) -CX (2,4) C motifs. [19] Notably, various constituents of the small and large subunit of cytoplasmic ribosomes, but also other factors involved in translation were identified to be sensitive to H 2 O 2 (Fig.   3d, right inset, Supplementary Data  6 ). [19] We found H 2 O 2 -sensitive motifs in the cytosolic translation apparatus, including several bona fide components of the ribosome and translation factors. [19] In further support of our proposal, the treatment of yeast cells with H 2 O 2 was previously shown to result in global and reversible translation reduction 36, 40, 51. [19] The treatment of HEK 293 cells with H 2 O 2 decreased translation in a concentration-dependent manner (Fig.   6b ). [19] H 2 O 2 treatment of cells inhibits TOR signalling, which can contribute to translation reduction. [19]

In eukaryotic cells, transcription happens inside the nucleus and translation can?t happen until the mRNA is transported out into the cytoplasm. [20] We site-specifically map redox-active cysteine residues as part of conserved sequence motifs in proteins of the translation machinery of the cell. [19] ROS induction reduces protein translation in the cytosol. a – e Incorporation of -labelled amino acids in yeast or mammalian cells. [19] Global cytosolic translation is known to be regulated under various stress conditions such as protein misfolding stress in the endoplasmic reticulum, UV irradiation, amino acid starvation, hypoxia, viral infections and oxidative stress 32 – 39. [19] Ribosomal proteins, proteins involved in ribosome biogenesis and in cytosolic translation were overrepresented in our analysis (Fig.   3e ). [19] Altogether, these findings supported our MS-based data, suggesting that ribosomal proteins can act as sensors for oxidative stress in order to mediate a decrease in translation. [19] Our data show that depletion of ribosomal proteins partially prevented translation attenuation. [19] Our study identifies a new mechanism that involves redox switches in the translation apparatus and functions to reversibly control protein translation under conditions of increased ROS generation, including mitochondria-derived pathologies. [19] Mechanisms underlying translation modulation mediated by oxidative changes in proteins appear to be more complex under endogenously elevated ROS levels originating from active mitochondria. [19]

If the elongation or termination of translation are blocked, nascent chains, which are removed by the ribosome quality control mechanisms and degraded 46, 47, should be recovered upon proteasomal inhibition. [19] Our data suggest a mechanism involved in translation inhibition upon oxidative stress, which is distinct from TOR regulation and acts via inhibition of translation elongation or termination. [19]

Outline the role of complementary base pairing between mRNA and tRNA in translation. [21] Outline the process of translation elongation, including codon recognition, bond formation and translocation. [22] Prokaryotes have no membrane bound organelles such as a nucleus, thus the process of transcription and translation can occur simultaneously. [20] The process of translation remodelling can be mediated by reversible changes in the redox state of components involved in protein synthesis that are susceptible to oxidation (Supplementary Fig.   7f ). [19]

Closer inspection of the redox-sensitive thiols in proteins involved in cytosolic translation revealed that virtually all contain CX 2 C-X (9–47) -CX (2,4) C sequence motifs (Table  1 ). [19] The redoxome analysis of yeast with elevated mitochondrial ROS production and decreased cytosolic translation revealed changes in the redox status of various proteins important for the synthesis of proteins. [19] Mapping of redox-active thiols in proteins exposed to exogenous or endogenous mitochondria-derived oxidative stress reveals ROS-sensitive sites in several components of the translation apparatus. [19] We studied published structures of proteins that are active in translation and contain this motif. [19] We now show that the inhibitory effect on translation was caused by increased ROS that are overproduced due to inefficient mitochondrial protein biogenesis. [19] Our data suggest that the translation apparatus is equipped with conserved, redox-sensitive switches to directly respond to increased levels of ROS, a hallmark of defective mitochondria, by decreasing the load of newly synthesised proteins. [19]

Most importantly, phosphorylation of eIF2α was decreased in the mia40-4int mutant under restrictive temperature (37 °C) compared with wild-type cells (Fig.   7c ), and thus this phosphorylation-dependent mechanism cannot contribute to the translation attenuation. [19] We constitutively expressed cysteine mutant forms of RPL40A -C115 (C115 was found to be sensitive to oxidative stress in our redoxome analyses; Fig.   5, Supplementary Fig.   3b and Supplementary Data  6 and 7 ) in wild-type yeast cells and analysed changes in translation (Supplementary Fig.   5h ). [19] The translation inhibition response was less pronounced for the cells with the RPL40A -C115S form (Supplementary Fig.   1h ). [19] When the mia40-4int cells were treated with the antioxidant NAC, translation was partially restored (Supplementary Fig.   6d ). [19] We applied NAC to mammalian cells to rescue the translation defect upon oxidative stress. [19] We asked whether the effect of oxidative stress on translation in yeast is also present in mammalian cells. [19] Recently, others and we discovered that cytosolic translation is modulated in cells harbouring defective mitochondria 27, 28. [19] A decrease in global translation is a general response of the cell to various stress conditions 32 – 39. [19] Translation was fully restored in these cells (Fig.   7f ). [19] Cells use ROS species to signal endogenous stress derived from mitochondrial dysfunction to regulate cytosolic translation in a reversible manner. [19]

We propose a universal mechanism that controls protein synthesis by inducing reversible changes in the translation machinery upon modulating the redox status of proteins involved in translation. [19] Therefore, more work will be needed to decipher exact molecular changes in the translation machinery that ultimately result in a halt in protein synthesis. [19] Ribosomal proteins can act as sensors for oxidative stress mediating a decrease in protein synthesis by pausing the translation at the post-initiation stage. [19] To address the issue whether there is a causal dependence between ROS and translation inhibition, we investigated whether ROS are sufficient to cause a decrease in protein synthesis. [19] Why are transcription and translation coupled in prokaryotes? To put it simply because they don?t have a nucleus. [20] Compare the timing and location of transcription and translation between prokaryotes and eukaryotes. [22] Liu L, Simon MC. Regulation of transcription and translation by hypoxia. [19]

At a glance, eukaryotes have overwhelmingly greater complexity, and a lot of this comes from RNA interactions before translation. [20] Simultaneous H 2 O 2 treatment had an additive effect on translation attenuation (Supplementary Fig.   7c ), suggesting the involvement of additional mTOR-independent mechanisms mediated by oxidative stress. [19] Global translation was reduced with increased concentration of H 2 O 2 in two different wild-type yeast strains (Fig.   6a and Supplementary Fig.   5a ). [19] Ebselen, a compound acting as a mimic of glutathione peroxidase 30, 31, partially restored translation upon H 2 O 2 treatment in wild-type yeast (Supplementary Fig.   6b ). [19] Upon H 2 O 2 treatment, 4E-BP1 was less phosphorylated resulting in stronger binding of eIF4E and inhibition of translation, indicative for mTOR pathway inhibition (Supplementary Fig.   7b ). [19] In yeast, mutants with deletions of TOR1 (component of TOR complex 1), SCH9 (homologue of S6 kinase) or TIF3 (homologue of eIF4B and target of Sch9) 45 showed higher translation compared to wild-type control upon H 2 O 2 treatment. [19]

Identify the sense and antisense strands of DNA given a diagram of translation. [21] Translation was still drastically reduced compared to untreated samples (Supplementary Fig.   7d ), consistently pointing to an additional TOR-independent mechanism. [19] These results are consistent with the hypothesis that the production of ROS by defective mitochondria is a cause of translation inhibition. [19] Our results show that oxidative stress itself is sufficient to block cytosolic translation and this can be reversed once physiological conditions are restored. [19]

Outline the process of translation termination, including the role of the stop codon. [22] A native protein inhibitor, eIF4E-binding protein 1 (4E-BP1), when phosphorylated, releases eIF4E for translation initiation. [19] Translation initiation block is not responsible for inhibitory effect of ROS. a,  b,  d – f Incorporation of -labelled amino acids in yeast or mammalian cells. [19] Translation initiation is often inhibited via the phosphorylation of the eukaryotic initiation factor 2α (eIF2α) 32. [19] Inhibition of mammalian target of rapamycin (mTOR) pathway was shown to regulate translation via multiple ways including inhibition of eukaryotic translation initiation factor 4 (eIF4E) 43. [19]

Sonenberg N, Hinnebusch AG. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. [19] Llacer JL, et al. Conformational differences between open and closed states of the eukaryotic translation initiation complex. [19]

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1. (54) Quantitative proteomics identifies redox switches for global translation modulation by mitochondrially produced reactive oxygen species

2. (49) Dual function of UPF3B in early and late translation termination | The EMBO Journal

3. (47) Translation (biology) - an overview | ScienceDirect Topics

4. (31) Multiple RNA structures affect translation initiation and UGA redefinition efficiency during synthesis of selenoprotein P | Nucleic Acids Research | Oxford Academic

5. (12) Transcription & Translation | Basic Biology

6. (12) DNA Translation

7. (11) Genetic code - Wikipedia

8. (9) Translation of DNA - Initiation - Elongation - Termination - TeachMePhysiology

9. (6) Translation: Making Protein Synthesis Possible

10. (6) The Transcription and Translation Process: Biology 101 Lesson Plans - Videos & Lessons | Study.com

11. (5) BOLO Biology Newsletter Archive: Translation

12. (5) Requirements for Translation | Biology for Non-Majors I

13. (4) Why are transcription and translation coupled in prokaryotes? - Quora

14. (3) How does protein synthesis take place in a cell? | Socratic

15. (3) Definition of transcription - NCI Dictionary of Cancer Terms - National Cancer Institute

16. (3) Translation - BIOLOGY FOR LIFE

17. (2) In Vitro Transcription / Translation | Biocompare.com

18. (2) Biology 151 - Transcription, Translation, amino acids. proteins Flashcards | Quizlet

19. (2) Replication, Transcription and Translation - BIOLOGY FOR LIFE

20. (2) Protein Production: A Simple Summary of Transcription and Translation | Owlcation

21. (2) How to Translate MRNA to TRNA | Sciencing

22. (1) biology translation French | English-French dictionary | Reverso

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