translational peptide chain termination


Summary: A process of GENETIC TRANSLATION whereby the terminal amino acid is added to a lengthening polypeptide. This termination process is signaled from the MESSENGER RNA, by one of three termination codons (CODON, TERMINATOR) that immediately follows the last amino acid-specifying CODON.

Top Publications

  1. Salas Marco J, Bedwell D. Discrimination between defects in elongation fidelity and termination efficiency provides mechanistic insights into translational readthrough. J Mol Biol. 2005;348:801-15 pubmed
    ..We used this misincorporation reporter in conjunction with a readthrough reporter system to show that alterations at different regions of the ribosome influence elongation fidelity and termination efficiency to different extents. ..
  2. Dontsova M, Frolova L, Vassilieva J, Piendl W, Kisselev L, Garber M. Translation termination factor aRF1 from the archaeon Methanococcus jannaschii is active with eukaryotic ribosomes. FEBS Lett. 2000;472:213-6 pubmed
    ..This observation confirms the earlier prediction that eRF1 and aRF1 form a common structural-functional eRF1/aRF1 protein family, originating from a common ancient ancestor...
  3. Stansfield I, Jones K, Kushnirov V, Dagkesamanskaya A, Poznyakovski A, Paushkin S, et al. The products of the SUP45 (eRF1) and SUP35 genes interact to mediate translation termination in Saccharomyces cerevisiae. EMBO J. 1995;14:4365-73 pubmed
  4. Zhouravleva G, Frolova L, Le Goff X, Le Guellec R, Inge Vechtomov S, Kisselev L, et al. Termination of translation in eukaryotes is governed by two interacting polypeptide chain release factors, eRF1 and eRF3. EMBO J. 1995;14:4065-72 pubmed
    ..It is proposed that a quaternary complex composed of eRF1, eRF3, GTP and a stop codon of the mRNA is involved in termination of polypeptide synthesis in ribosomes. ..
  5. Gao N, Zavialov A, Li W, Sengupta J, Valle M, Gursky R, et al. Mechanism for the disassembly of the posttermination complex inferred from cryo-EM studies. Mol Cell. 2005;18:663-74 pubmed publisher
    ..These observations provide the structural basis for the mechanism by which the posttermination complex is split into subunits by the joint action of RRF and EF-G...
  6. Laurberg M, Asahara H, Korostelev A, Zhu J, Trakhanov S, Noller H. Structural basis for translation termination on the 70S ribosome. Nature. 2008;454:852-7 pubmed publisher
    ..Unexpectedly, the main-chain amide group of Gln 230 in the universally conserved GGQ motif of the factor is positioned to contribute directly to peptidyl-tRNA hydrolysis. ..
  7. Funakoshi Y, Doi Y, Hosoda N, Uchida N, Osawa M, Shimada I, et al. Mechanism of mRNA deadenylation: evidence for a molecular interplay between translation termination factor eRF3 and mRNA deadenylases. Genes Dev. 2007;21:3135-48 pubmed
    ..Consequently, PABPC1 binding leads to the activation of Pan2-Pan3 and Caf1-Ccr4. From these results, we suggest a mechanism of mRNA deadenylation by Pan2-Pan3 and Caf1-Ccr4 in cooperation with eRF3 and PABPC1. ..
  8. Hatin I, Fabret C, Namy O, Decatur W, Rousset J. Fine-tuning of translation termination efficiency in Saccharomyces cerevisiae involves two factors in close proximity to the exit tunnel of the ribosome. Genetics. 2007;177:1527-37 pubmed
    ..Among them, SSB1 and snR18, two factors close to the exit tunnel of the ribosome, directed the strongest antisuppression effects when overexpressed, showing that they may be involved in fine-tuning of the translation termination level. ..
  9. Zhang Y, Spremulli L. Identification and cloning of human mitochondrial translational release factor 1 and the ribosome recycling factor. Biochim Biophys Acta. 1998;1443:245-50 pubmed
    ..The complete cDNA for the human mitochondrial ribosome recycling factor has been assembled using EST clones. This factor has been expressed in Escherichia coli and purified as a His-tagged protein. ..

More Information


  1. Mora L, Heurgué Hamard V, de Zamaroczy M, Kervestin S, Buckingham R. Methylation of bacterial release factors RF1 and RF2 is required for normal translation termination in vivo. J Biol Chem. 2007;282:35638-45 pubmed
    ..This suggests that the expression of some genes needed for optimal growth under such conditions can become growth limiting as a result of inefficient translation termination. ..
  2. Ozawa Y, Saito R, Washio T, Tomita M. Comparative study of translation termination sites and release factors (RF1 and RF2) in procaryotes. J Mol Evol. 2003;56:665-72 pubmed
    ..In addition, some of the residues were located very close to the SPF motif, which deciphers stop codons. These results suggest that these conserved amino acids enable the release factors to recognize the bases around the stop codons. ..
  3. Klaholz B, Myasnikov A, Van Heel M. Visualization of release factor 3 on the ribosome during termination of protein synthesis. Nature. 2004;427:862-5 pubmed
    ..Because state 1 seems able to accommodate simultaneously both RF3 and RF2, whose position is known from previous studies, we can infer the release mechanism of class I RFs. ..
  4. Zhang S, Ryden Aulin M, Isaksson L. Functional interaction between release factor one and P-site peptidyl-tRNA on the ribosome. J Mol Biol. 1996;261:98-107 pubmed
    ..The data suggest that RF1-mediated termination at UAG is sensitive to the nature of the codon-anticodon interaction of the wobble base, the last amino acid residue of the nascent peptide chain, and the tRNA at the ribosomal P-site. ..
  5. Merkulova T, Frolova L, Lazar M, Camonis J, Kisselev L. C-terminal domains of human translation termination factors eRF1 and eRF3 mediate their in vivo interaction. FEBS Lett. 1999;443:41-7 pubmed
    ..The human eRF1 lacking 22 C-terminal amino acids remains active as a release factor and promotes an eRF3 GTPase activity whereas C-terminally truncated eRF3 is inactive as a GTPase. ..
  6. Oparina N, Kalinina O, Gelfand M, Kisselev L. Common and specific amino acid residues in the prokaryotic polypeptide release factors RF1 and RF2: possible functional implications. Nucleic Acids Res. 2005;33:5226-34 pubmed
    ..Presumably, they also take part in stop codon binding and discrimination. Elucidation of potential functional role(s) of the newly identified SDP/IR zones requires further experiments. ..
  7. Kisselev L. Translation termination and yeast prions. Biochemistry (Mosc). 1999;64:1337-41 pubmed
    ..This issue of Biochemistry (Moscow) highlights from various points of view the problem of translation termination, excluding protein folding. Yeast termination factors with prion-like properties are also considered. ..
  8. Alkalaeva E, Pisarev A, Frolova L, Kisselev L, Pestova T. In vitro reconstitution of eukaryotic translation reveals cooperativity between release factors eRF1 and eRF3. Cell. 2006;125:1125-36 pubmed
    ..Cooperativity between eRF1 and eRF3 required the eRF3 binding C-terminal domain of eRF1. ..
  9. Dincbas Renqvist V, Engstrom A, Mora L, Heurgué Hamard V, Buckingham R, Ehrenberg M. A post-translational modification in the GGQ motif of RF2 from Escherichia coli stimulates termination of translation. EMBO J. 2000;19:6900-7 pubmed
    ..We propose that the previously observed lethal effect of overproducing E.coli K12 RF2 arises through accumulating the defects due to lack of Gln252 methylation and Thr246 in place of alanine. ..
  10. Isken O, Grassmann C, Yu H, Behrens S. Complex signals in the genomic 3' nontranslated region of bovine viral diarrhea virus coordinate translation and replication of the viral RNA. RNA. 2004;10:1637-52 pubmed
    ..Our data suggest the accuracy of translation termination as a sophisticated device determining viral adaptation to the host. ..
  11. Le Roy F, Salehzada T, Bisbal C, Dougherty J, Peltz S. A newly discovered function for RNase L in regulating translation termination. Nat Struct Mol Biol. 2005;12:505-12 pubmed
    ..On the basis of our results, we present a model describing how RNase L is involved in regulating gene expression by modulating the translation termination process. ..
  12. Hoshino S, Imai M, Kobayashi T, Uchida N, Katada T. The eukaryotic polypeptide chain releasing factor (eRF3/GSPT) carrying the translation termination signal to the 3'-Poly(A) tail of mRNA. Direct association of erf3/GSPT with polyadenylate-binding protein. J Biol Chem. 1999;274:16677-80 pubmed
    ..Thus, the present study is the first report showing that GSPT/eRF3 carries the translation termination signal to 3'-poly(A) tail ubiquitously present in eukaryotic mRNAs. ..
  13. Mora L, Heurgué Hamard V, Champ S, Ehrenberg M, Kisselev L, Buckingham R. The essential role of the invariant GGQ motif in the function and stability in vivo of bacterial release factors RF1 and RF2. Mol Microbiol. 2003;47:267-75 pubmed
  14. Kisselev L, Buckingham R. Translational termination comes of age. Trends Biochem Sci. 2000;25:561-6 pubmed
    ..Post-termination events in bacteria have been clarified, linking termination, ribosomal recycling and translation initiation. ..
  15. Keeling K, Salas Marco J, Osherovich L, Bedwell D. Tpa1p is part of an mRNP complex that influences translation termination, mRNA deadenylation, and mRNA turnover in Saccharomyces cerevisiae. Mol Cell Biol. 2006;26:5237-48 pubmed
    ..These results suggest that Tpa1p is a component of a messenger ribonucleoprotein complex bound to the 3' untranslated region of mRNAs that affects translation termination, deadenylation, and mRNA decay. ..
  16. Feinberg J, Joseph S. A conserved base-pair between tRNA and 23 S rRNA in the peptidyl transferase center is important for peptide release. J Mol Biol. 2006;364:1010-20 pubmed
  17. Ivanova E, Kolosov P, Birdsall B, Kelly G, Pastore A, Kisselev L, et al. Eukaryotic class 1 translation termination factor eRF1--the NMR structure and dynamics of the middle domain involved in triggering ribosome-dependent peptidyl-tRNA hydrolysis. FEBS J. 2007;274:4223-37 pubmed
  18. Pavlov M, Freistroffer D, Heurgué Hamard V, Buckingham R, Ehrenberg M. Release factor RF3 abolishes competition between release factor RF1 and ribosome recycling factor (RRF) for a ribosome binding site. J Mol Biol. 1997;273:389-401 pubmed
    ..The overproduction of RF1 in cells deficient in RRF or lacking RF3 has effects on growth rate predicted by the in vitro experiments. ..
  19. Buckingham R, Grentzmann G, Kisselev L. Polypeptide chain release factors. Mol Microbiol. 1997;24:449-56 pubmed
    ..e. RF3 and eRF3. ..
  20. Powell M, Napthine S, Jackson R, Brierley I, Brown T. Characterization of the termination-reinitiation strategy employed in the expression of influenza B virus BM2 protein. RNA. 2008;14:2394-406 pubmed publisher
    ..This suggests that the full complement of initiation factors is not required for the reinitiation process. ..
  21. Luttermann C, Meyers G. The importance of inter- and intramolecular base pairing for translation reinitiation on a eukaryotic bicistronic mRNA. Genes Dev. 2009;23:331-44 pubmed publisher
    ..Analysis of the essential elements of the TURBS led to a better understanding of the requirements for translation termination/reinitiation in eukaryotes. ..
  22. Powell M, Brown T, Brierley I. Translational termination-re-initiation in viral systems. Biochem Soc Trans. 2008;36:717-22 pubmed publisher
  23. Hatin I, Fabret C, Rousset J, Namy O. Molecular dissection of translation termination mechanism identifies two new critical regions in eRF1. Nucleic Acids Res. 2009;37:1789-98 pubmed publisher
    ..Our findings are consistent with the model of a closed-active conformation of eRF1 and shed light on two new functional regions of the protein. ..
  24. Stansfield I, Grant G, Akhmaloka -, Tuite M. Ribosomal association of the yeast SAL4 (SUP45) gene product: implications for its role in translation fidelity and termination. Mol Microbiol. 1992;6:3469-78 pubmed
    ..In view of these data, and given the stoichiometry of Sal4p to individual ribosomal proteins (estimated at less than 1:20), we suggest that Sal4p plays an ancillary role in translation termination. ..
  25. Martin R, Weiner M, Gallant J. Effects of release factor context at UAA codons in Escherichia coli. J Bacteriol. 1988;170:4714-7 pubmed
    ..We show here that the activity of RF1 and RF2 varies according to messenger context. RF1 is favored at UAA codons which are efficiently suppressed. RF2 is preferred at poorly suppressed sites. ..
  26. Janosi L, Ricker R, Kaji A. Dual functions of ribosome recycling factor in protein biosynthesis: disassembling the termination complex and preventing translational errors. Biochimie. 1996;78:959-69 pubmed
    ..Finally, we review the known RRF sequences from various organisms including eukaryotes and discuss the possible mechanism for disassembly of the eukaryotic termination complex. ..
  27. Freistroffer D, Kwiatkowski M, Buckingham R, Ehrenberg M. The accuracy of codon recognition by polypeptide release factors. Proc Natl Acad Sci U S A. 2000;97:2046-51 pubmed
    ..Two codons, UAU and UGG, stand out as hotspots for RF-dependent premature termination. ..
  28. Valouev I, Urakov V, Kochneva Pervukhova N, Smirnov V, Ter Avanesyan M. Translation termination factors function outside of translation: yeast eRF1 interacts with myosin light chain, Mlc1p, to effect cytokinesis. Mol Microbiol. 2004;53:687-96 pubmed
    ..The data obtained demonstrate that yeast eRF1 has an important non-translational function effecting cytokinesis via interaction with Mlc1p. ..
  29. Ito K, Ebihara K, Nakamura Y. The stretch of C-terminal acidic amino acids of translational release factor eRF1 is a primary binding site for eRF3 of fission yeast. RNA. 1998;4:958-72 pubmed
    ..These results cannot be accounted for by the simple "eRF3-EF-Tu mimicry" model, but may provide new insight into the eRF3 function for translation termination in eukaryotes. ..
  30. Mitkevich V, Kononenko A, Petrushanko I, Yanvarev D, Makarov A, Kisselev L. Termination of translation in eukaryotes is mediated by the quaternary eRF1*eRF3*GTP*Mg2+ complex. The biological roles of eRF3 and prokaryotic RF3 are profoundly distinct. Nucleic Acids Res. 2006;34:3947-54 pubmed
    ..The guanine nucleotide binding properties of eRF3 and of the eRF3*eRF1 complex profoundly differ from those of prokaryotic RF3. ..
  31. Polacek N, Gomez M, Ito K, Xiong L, Nakamura Y, Mankin A. The critical role of the universally conserved A2602 of 23S ribosomal RNA in the release of the nascent peptide during translation termination. Mol Cell. 2003;11:103-12 pubmed
    ..This indicates that the mechanism of peptide release is distinct from that of peptide bond formation, with A2602 playing a critical role in peptide release during translation termination. ..
  32. Salas Marco J, Bedwell D. GTP hydrolysis by eRF3 facilitates stop codon decoding during eukaryotic translation termination. Mol Cell Biol. 2004;24:7769-78 pubmed
    ..Together, these results suggest that the GTPase activity of eRF3 is required to couple the recognition of translation termination signals by eRF1 to efficient polypeptide chain release. ..
  33. Kapp L, Lorsch J. The molecular mechanics of eukaryotic translation. Annu Rev Biochem. 2004;73:657-704 pubmed
    ..We discuss the mechanisms conserved across the three kingdoms of life as well as the important divergences that have taken place in the pathway. ..
  34. Keeling K, Lanier J, Du M, Salas Marco J, Gao L, Kaenjak Angeletti A, et al. Leaky termination at premature stop codons antagonizes nonsense-mediated mRNA decay in S. cerevisiae. RNA. 2004;10:691-703 pubmed
    ..5%. This low threshold for the onset of the major component of NMD indicates that mRNA surveillance is an ongoing process that occurs throughout the lifetime of an mRNA. ..
  35. Nakamura Y, Ito K, Isaksson L. Emerging understanding of translation termination. Cell. 1996;87:147-50 pubmed
  36. Dincbas V, Heurgué Hamard V, Buckingham R, Karimi R, Ehrenberg M. Shutdown in protein synthesis due to the expression of mini-genes in bacteria. J Mol Biol. 1999;291:745-59 pubmed
    ..It is proposed that the retranslation by ribosomes of mini-gene transcripts with efficient ribosome binding (Shine/Dalgarno) sequences strongly contributes to the inhibitory effects of mini-gene expression on protein synthesis. ..
  37. Urakov V, Valouev I, Kochneva Pervukhova N, Packeiser A, Vishnevsky A, Glebov O, et al. N-terminal region of Saccharomyces cerevisiae eRF3 is essential for the functioning of the eRF1/eRF3 complex beyond translation termination. BMC Mol Biol. 2006;7:34 pubmed
    ..These and other data demonstrate that the N-terminal region of eRF3 is involved both in modulation of the efficiency of translation termination and functioning of the eRF1/eRF3 complex outside of translation termination. ..
  38. Amrani N, Ganesan R, Kervestin S, Mangus D, Ghosh S, Jacobson A. A faux 3'-UTR promotes aberrant termination and triggers nonsense-mediated mRNA decay. Nature. 2004;432:112-8 pubmed
    ..These findings indicate that efficient termination and mRNA stability are dependent on a properly configured 3'-UTR. ..
  39. Frolova L, Seit Nebi A, Kisselev L. Highly conserved NIKS tetrapeptide is functionally essential in eukaryotic translation termination factor eRF1. RNA. 2002;8:129-36 pubmed
    ..Reduction in ribosome binding revealed for Ile62, Ser64, Arg65, and Arg68 mutants argues in favor of the essential role played by the right part of the NIKS loop in interaction with the ribosome, most probably with ribosomal RNA. ..
  40. Rospert S, Rakwalska M, Dubaquie Y. Polypeptide chain termination and stop codon readthrough on eukaryotic ribosomes. Rev Physiol Biochem Pharmacol. 2005;155:1-30 pubmed
    ..This review explores our current understanding of eukaryotic termination by highlighting the roles of the different ribosomal components as well as termination factors and ribosome-associated proteins, such as chaperones. ..
  41. Beier H, Grimm M. Misreading of termination codons in eukaryotes by natural nonsense suppressor tRNAs. Nucleic Acids Res. 2001;29:4767-82 pubmed
    ..It is discussed that not only RNA viruses, but also the eukaryotic host organism might gain some profit from cellular suppressor tRNAs...
  42. Song H, Mugnier P, Das A, Webb H, Evans D, Tuite M, et al. The crystal structure of human eukaryotic release factor eRF1--mechanism of stop codon recognition and peptidyl-tRNA hydrolysis. Cell. 2000;100:311-21 pubmed
    ..A conserved groove on domain 1, 80 A from the GGQ motif, is proposed to form the codon recognition site. ..
  43. Cruz Vera L, Magos Castro M, Zamora Romo E, Guarneros G. Ribosome stalling and peptidyl-tRNA drop-off during translational delay at AGA codons. Nucleic Acids Res. 2004;32:4462-8 pubmed
    ..These and previous results support the hypothesis that the primary mechanism of inhibition of protein synthesis by AGA triplets in pth+ cells involves sequestration of tRNAs as peptidyl-tRNA on the stalled ribosome. ..
  44. Trobro S, Aqvist J. A model for how ribosomal release factors induce peptidyl-tRNA cleavage in termination of protein synthesis. Mol Cell. 2007;27:758-66 pubmed
    ..This model explains key mutation experiments and shows that the ribosomal peptidyl transfer center catalyzes its two chemical reactions by a common mechanism. ..
  45. Janosi L, Mottagui Tabar S, Isaksson L, Sekine Y, Ohtsubo E, Zhang S, et al. Evidence for in vivo ribosome recycling, the fourth step in protein biosynthesis. EMBO J. 1998;17:1141-51 pubmed
    ..RRF inactivation was bacteriostatic in the growing phase and bactericidal during the transition between the stationary and growing phase, confirming the essential nature of the fourth step of protein synthesis in vivo. ..
  46. Fan Minogue H, Du M, Pisarev A, Kallmeyer A, Salas Marco J, Keeling K, et al. Distinct eRF3 requirements suggest alternate eRF1 conformations mediate peptide release during eukaryotic translation termination. Mol Cell. 2008;30:599-609 pubmed publisher
    ..These results suggest that the TASNIKS motif and eRF3 function together to trigger eRF1 conformational changes that couple stop codon recognition and peptide release during eukaryotic translation termination...
  47. Hauryliuk V, Zavialov A, Kisselev L, Ehrenberg M. Class-1 release factor eRF1 promotes GTP binding by class-2 release factor eRF3. Biochimie. 2006;88:747-57 pubmed
  48. Gross T, Siepmann A, Sturm D, Windgassen M, Scarcelli J, Seedorf M, et al. The DEAD-box RNA helicase Dbp5 functions in translation termination. Science. 2007;315:646-9 pubmed
    ..Therefore, Dbp5 controls the eRF3-eRF1 interaction and thus eRF3-mediated downstream events. ..
  49. Heurgué Hamard V, Karimi R, Mora L, MacDougall J, Leboeuf C, Grentzmann G, et al. Ribosome release factor RF4 and termination factor RF3 are involved in dissociation of peptidyl-tRNA from the ribosome. EMBO J. 1998;17:808-16 pubmed
    ..It is suggested that RF4 may displace peptidyl-tRNA from the ribosome in a manner related to its proposed function in removing deacylated tRNA during ribosome recycling. ..
  50. Gavini N, Pulakat L. Role of ribosome release in the basal level of expression of the Escherichia coli gene pheA. J Gen Microbiol. 1991;137:679-84 pubmed
    ..These results support the proposal that the release of translating ribosomes from the leader peptide stop codon in stem 2 of the pheA attenuator plays a crucial role in determining the basal level of expression of this gene. ..
  51. Hirokawa G, Kiel M, Muto A, Selmer M, Raj V, Liljas A, et al. Post-termination complex disassembly by ribosome recycling factor, a functional tRNA mimic. EMBO J. 2002;21:2272-81 pubmed publisher
    ..With the model post-termination complex, 70S ribosomes were released from the post-termination complex by the RRF reaction and were then dissociated into subunits by IF3...
  52. Matsumura K, Ito K, Kawazu Y, Mikuni O, Nakamura Y. Suppression of temperature-sensitive defects of polypeptide release factors RF-1 and RF-2 by mutations or by an excess of RF-3 in Escherichia coli. J Mol Biol. 1996;258:588-99 pubmed
    ..Taking these and other results into consideration, RF-3 is likely to interact functionally and cooperatively with the release factors RF-1 and RF-2 in Escherichia coli. ..
  53. Raney A, Law G, Mize G, Morris D. Regulated translation termination at the upstream open reading frame in s-adenosylmethionine decarboxylase mRNA. J Biol Chem. 2002;277:5988-94 pubmed
    ..This regulation may involve an interaction between the peptide, polyamines, and a target in the translational apparatus. ..