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RAS BiologyМолекулярная биология Molecular Biology

  • ISSN (Print) 0026-8984
  • ISSN (Online) 3034-5553

The CCC Proline Codon Preceding a Stop Codon Modulates Translation Termination in Eukaryotes Depending on the Molecular Context

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PII
S30345553S0026898425040056-1
DOI
10.7868/S3034555325040056
Publication type
Article
Status
Published
Authors
N.S. Biziaev
  • Affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
A.V. Shuvalov
  • Affiliation:
    Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
    Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
E.Z. Alkalaeva
  • Affiliation:
    Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
    Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Volume/ Edition
Volume 59 / Issue number 4
Pages
587-598
Abstract
In bacteria, glycine and proline codons located upstream of stop codons suppress translation termination. However, the effects of these codons in eukaryotes have not been systematically studied. This work demonstrates that the CCC codon of proline preceding a stop codon slows down eukaryotic translation termination when synthesizing a long protein. On the contrary, when synthesizing a short peptide, the proline codon in this position stimulates the formation of termination complexes. Additionally, the role of one of the main regulators of eukaryotic translation termination, the poly(A)-binding protein (PABP), which binds to the poly(A) tail of mRNA, was described in the modulation of translation termination by the 5'-context of the stop codon. It was found that during the synthesis of a short peptide, PABP reduces the dependence of translation termination on the influence of the 5'-contexts of stop codons, while during the synthesis of a long protein, it stimulates translation termination regardless of the 5'-context of the stop codon.
Keywords
терминация трансляции eRF1 eRF3 5'-контекст стоп-кодона PABP
Date of publication
31.01.2026
Year of publication
2026
Number of purchasers
0
Views
73

References

  1. 1. Alkalaeva E.Z., Pisarev A.V., Frolova L.Y., Kisselev L.L., Pestova T.V. (2006) In vitro reconstitution of eukaryotic translation reveals cooperativity between release factors eRF1 and eRF3. Cell. 125, 1125–1136.
  2. 2. Hellen C.U.T. (2018) Translation termination and ribosome recycling in eukaryotes. Cold Spring Harbor Persp. Biol. 10, I. 10. 1–18.
  3. 3. Egorova T., Biziaev N., Shuvalov A., Sokolova E., Mukba S., Evmenov K., Zotova M., Kushchenko A., Shuvalova E., Alkalaeva E. (2021) eIF3j facilitates loading of release factors into the ribosome. Nucl. Acids Res. 49, 11181–11196.
  4. 4. Ivanov A., Mikhailova T., Eliseev B., Yeramala L., Sokolova E., Susorov D., Shuvalov A., Schaffitzel C., Alkalaeva E. (2016) PABP enhances release factor recruitment and stop codon recognition during translation termination. Nucl. Acids Res. 44, 7766–7776.
  5. 5. Biziaev N., Shuvalov A., Salman A., Egorova T., Shuvalova E., Alkalaeva E. (2024) The impact of mRNA poly(A) tail length on eukaryotic translation stages. Nucl. Acids Res. 52, 7792–7808.
  6. 6. Wu C., Roy B., He F., Yan K., Jacobson A. (2020) Poly(A)-binding protein regulates the efficiency of translation termination. Cell Rep. 33, 108399.
  7. 7. Ivanov P.V., Gehring N.H., Kunz J.B., Hentze M.W., Kulozik A.E. (2008) Interactions between UPF1, eRFs, PABP and the exon junction complex suggest an integrated model for mammalian NMD pathways. EMBO J. 27, 736–747.
  8. 8. Cosson B., Berkova N., Couturier A., Chabelskaya S., Philippe M., Zhouravleva G. (2002) Poly(A)-binding protein and eRF3 are associated in vivo in human and Xenopus cells. Biol. Cell. 94, 205–216.
  9. 9. Hoshino S., Imai M., Kobayashi T., Uchida N., Katada T. (1999) The eukaryotic polypeptide chain releasing factor (eRF3/GSPT) carrying the translation termination signal to the 3ʹ-poly(A) tail of mRNA. J. Biol. Chem. 274, 16677–16680.
  10. 10. Uchida N., Hoshino S., Imataka H., Sonenberg N., Katada T. (2002) A novel role of the mammalian GSPT/eRF3 associating with poly(A)-binding protein in cap/poly(A)-dependent translation. J. Biol. Chem. 277, 50286–50292.
  11. 11. Бизяев Н.С., Егорова Т.В., Алкалаева Е.З. (2022) Динамика структуры мРНК эукариот в ходе трансляции. Молекуляр. биология. 56, 451–464.
  12. 12. Lima S.A., Chipman L.B., Nicholson A.L., Chen Y.H., Yee B.A., Yeo G.W., Coller J., Pasquinelli A.E. (2017) Short poly(A) tails are a conserved feature of highly expressed genes. Nat. Struct. Mol. Biol. 24, 1057–1063.
  13. 13. Beier H., Grimm M. (2001) Misreading of termination codons in eukaryotes by natural nonsense suppressor tRNAs. Nucl. Acids Res. 29, 4767–4782.
  14. 14. Bertram G., Innes S., Minella O., Richardson J., Stansfield I. (2001) Endless possibilities: translation termination and stop codon recognition. Microbiology. 147, 255–269.
  15. 15. Roy B., Leszyk J.D., Mangus D.A., Jacobson A. (2015) Nonsense suppression by near-cognate tRNAs employs alternative base pairing at codon positions 1 and 3. Proc. Natl. Acad. Sci. USA. 112, 3038–3043.
  16. 16. Vallabhaneni H., Fan-Minogue H., Bedwell D.M., Farabaugh P.J. (2009) Connection between stop codon reassignment and frequent use of shifty stop frameshifting. RNA. 15, 889–897.
  17. 17. Kurian L., Palanimurugan R., Gödderz D., Dohmen R.J. (2011) Polyamine sensing by nascent ornithine decarboxylase antizyme stimulates decoding of its mRNA. Nature. 477, 490–494.
  18. 18. Amrani N., Sachs M.S., Jacobson A. (2006) Early nonsense: mRNA decay solves a translational problem. Nat. Rev. Mol. Cell. Biol. 7, 415–425.
  19. 19. Celik A., Kervestin S., Jacobson A. (2015) NMD: at the crossroads between translation termination and ribosome recycling. Biochimie. 114, 2–9.
  20. 20. Raimondeau E., Bufton J.C., Schaffitzel C. (2018) New insights into the interplay between the translation machinery and nonsense-mediated mRNA decay factors. Biochem. Soc. Trans. 46, 503–512.
  21. 21. Embree C.M., Abu-Alhasan R., Singh G. (2022) Features and factors that dictate if terminating ribosomes cause or counteract nonsense-mediated mRNA decay. J. Biol. Chem. 298, 102592.
  22. 22. Соколова Е.Е., Власов П.К., Егорова Т.В., Шувалов А.В., Алкалаева Е.З. (2020) Влияние А/G-состава 3ʹ-контекстов стоп-кодонов на терминацию трансляции у эукариот. Молекуляр. биология. 54, 837–848.
  23. 23. Cridge A.G., Crowe-McAuliffe C., Mathew S.F., Tate W.P. (2018) Eukaryotic translational termination efficiency is influenced by the 3′ nucleotides within the ribosomal mRNA channel. Nucl. Acids Res. 46, 1927–1944.
  24. 24. Björnsson A., Mottagui-Tabar S., Isaksson L.A. (1996) Structure of the C-terminal end of the nascent peptide influences translation termination. EMBO J. 15, 1696–1704.
  25. 25. Mottagui-Tabar S., Tuite M.F., Isaksson L.A. (1998) The influence of 5’ codon context on translation termination in Saccharomyces cerevisiae. Eur. J.  Biochem. 257, 249–254.
  26. 26. Tork S., Hatin I., Rousset J.P., Fabret C. (2004) The major 5ʹ determinant in stop codon read-through involves two adjacent adenines. Nucl. Acids Res. 32, 415–421.
  27. 27. Wangen J.R., Green R. (2020) Stop codon context influences genome-wide stimulation of termination codon readthrough by aminoglycosides. ELife. 9, 1–29.
  28. 28. Dabrowski M., Bukowy-Bieryllo Z., Zietkiewicz E. (2015) Translational readthrough potential of natural termination codons in eucaryotes — The impact of RNA sequence. RNA Biol. 12, 950–958.
  29. 29. Cassan M., Rousset J.P. (2001) UAG readthrough in mammalian cells: effect of upstream and downstream stop codon contexts reveal different signals. BMC Mol. Biol. 2, article number 3, 1–8.
  30. 30. Bonetti B., Fu L., Moon J., Bedwell D.M. (1995) The efficiency of translation termination is determined by a synergistic interplay between upstream and downstream sequences in Saccharomyces cerevisiae. J. Mol. Biol. 251, 334–345.
  31. 31. Loughran G., Chou M.Y., Ivanov I.P., Jungreis I., Kellis M., Kiran A.M., Baranov P.V., Atkins J.F. (2014) Evidence of efficient stop codon readthrough in four mammalian genes. Nucl. Acids Res. 42, 8928–8938.
  32. 32. Williams I., Richardson J., Starkey A., Stansfield I. (2004) Genome-wide prediction of stop codon readthrough during translation in the yeast Saccharomyces cerevisiae. Nucl. Acids Res. 32, 6605–6616.
  33. 33. Bohlen J., Harbrecht L., Blanco S., Clemm von Hohenberg K., Fenzl K., Kramer G., Bukau B., Teleman A.A. (2020) DENR promotes translation reinitiation via ribosome recycling to drive expression of oncogenes including ATF4. Nat. Commun. 11, 4676, 1–15.
  34. 34. Young D.J., Meydan S., Guydosh N.R. (2021) 40S ribosome profiling reveals distinct roles for Tma20/Tma22 (MCT‑1/DENR) and Tma64 (eIF2D) in 40S subunit recycling. Nat. Commun. 12, 2976, 1–16.
  35. 35. Young D.J., Guydosh N.R. (2022) Rebirth of the translational machinery: the importance of recycling ribosomes. BioEssays. 44, 2100269, 1–16.
  36. 36. Kolakada D., Fu R., Biziaev N., Shuvalov A., Lore M., Campbell A.E., Cortázar M.A., Sajek M.P., Hesselberth J.R., Mukherjee N., Alkalaeva E., Coban-Akdemir Z.H., Jagannathan S. (2025) Systematic analysis of nonsense variants uncovers peptide release rate as a novel modifier of nonsense-mediated mRNA decay. Cell Genomics, 100882.
  37. 37. Pierson W.E., Hoffer E.D., Keedy H.E., Simms C.L., Dunham C.M., Zaher H.S. (2016) Uniformity of peptide release is maintained by methylation of release factors. Cell Rep. 17, 11–18.
  38. 38. Meydan S., Guydosh N.R. (2020) Disome and trisome profiling reveal genome-wide targets of ribosome quality control. Mol. Cell. 79, 588–602.e6.
  39. 39. Schuller A.P., Wu C.C.C., Dever T.E., Buskirk A.R., Green R. (2017) eIF5A functions globally in translation elongation and termination. Mol. Cell. 66, 194–205.e5.
  40. 40. Gutierrez E., Shin B.-S., Woolstenhulme C.J., Kim J.-R., Saini P., Buskirk A.R., Dever T.E. (2013) eIF5A promotes translation of polyproline motifs. Mol. Cell. 51, 35–45.
  41. 41. Schuller A.P., Green R. (2018) Roadblocks and resolutions in eukaryotic translation. Nat. Rev. Mol. Cell Biol. 19, 526–541.
  42. 42. Doerfel L.K., Wohlgemuth I., Kothe C., Peske F., Urlaub H., Rodnina M.V. (2013) EF-P is essential for rapid synthesis of proteins containing consecutive proline residues. Science. 339, 85–88.
  43. 43. Ude S., Lassak J., Starosta A.L., Kraxenberger T., Wilson D.N., Jung K. (2013) Translation elongation factor EF-P alleviates ribosome stalling at polyproline stretches. Science. 339, 82–85.
  44. 44. Pavlov M.Y., Watts R.E., Tan Z., Cornish V.W., Ehrenberg M., Forster A.C. (2009) Slow peptide bond formation by proline and other N-alkylamino acids in translation. Proc. Natl. Acad. Sci. USA. 106, 50–54.
  45. 45. Wohlgemuth I., Brenner S., Beringer M., Rodnina M.V. (2008) Modulation of the rate of peptidyl transfer on the ribosome by the nature of substrates. J. Biol. Chem. 283, 32229–32235.
  46. 46. Коростелев А.A. (2021) Различия и сходство процессов терминации трансляции и спасения рибосомы в бактериальных клетках и в митохондриях и цитоплазме эукариотических клеток. Биохимия. 86, 1328–1344.
  47. 47. Donnelly M.L.L., Luke G., Mehrotra A., Li X., Hughes L.E., Gani D., Ryan M.D. (2001) Analysis of the aphthovirus 2A/2B polyprotein “cleavage” mechanism indicates not a proteolytic reaction, but a novel translational effect: а putative ribosomal “skip.” J. Gen. Virol. 82, 1013–1025.
  48. 48. Sharma P., Yan F., Doronina V.A., Escuin-Ordinas H., Ryan M.D., Brown J.D. (2012) 2A peptides provide distinct solutions to driving stop-carry on translational recoding. Nucl. Acids Res. 40, 3143–3151.
  49. 49. Ito K., Chiba S. (2013) Arrest peptides: сis-acting modulators of translation. Annu. Rev. Biochem. 82, 171–202.
  50. 50. Shuvalov A., Shuvalova E., Biziaev N., Sokolova E., Evmenov K., Pustogarov N., Arnautova A., Matrosova V., Egorova T., Alkalaeva E. (2021) Nsp1 of SARS-CoV‑2 stimulates host translation termination. RNA Biol. 18, sup.2, 1–14.
  51. 51. Shuvalov A., Klishin A., Biziaev N., Shuvalova E., Alkalaeva E. (2024) Functional аctivity of isoform 2 of human eRF1. Internat. J. Mol. Sci. 25, 7997.
  52. 52. Susorov D., Egri S., Korostelev A.A. (2020) Termi-Luc: a versatile assay to monitor full-protein release from ribosomes. RNA. 26, 2044–2050.
  53. 53. Egorova T., Sokolova E., Shuvalova E., Matrosova V., Shuvalov A., Alkalaeva E. (2019) Fluorescent toeprinting to study the dynamics of ribosomal complexes. Methods. 162–163, 54–59.
  54. 54. Shirokikh N.E., Alkalaeva E.Z., Vassilenko K.S., Afonina Z.A., Alekhina O.M., Kisselev L.L., Spirin A.S. (2009) Quantitative analysis of ribosome-mRNA complexes at different translation stages. Nucl. Acids Res. 38. e15.
  55. 55. Holm S. (1979) A simple sequentially rejective multiple test procedure. Scandinavian J. Statistics. 6, 65–70.
  56. 56. Frolova L.Y., Tsivkovskii R.Y., Sivolobova G.F., Oparina N.Y., Serpinsky O.I., Blinov V.M., Tatkov S.I., Kisselev L.L. (1999) Mutations in the highly conserved GGQ motif of class I polypeptide release factors abolish ability of human eRF1 to trigger peptidyl-tRNA hydrolysis. RNA. 5, 1014–1020.
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