N1Methylpseudouridine directly modulates translation dynamics
Saxena, S. et al. The future of mRNA vaccines: potential beyond COVID-19. Cureus 17, e84529 (2025).
Anderson, B. R. et al. Nucleoside modifications in RNA limit activation of 2′−5′-oligoadenylate synthetase and increase resistance to cleavage by RNase L. Nucleic Acids Res. 39, 9329–9338 (2011).
Karikó, K. et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833–1840 (2008).
Andries, O. et al. N1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. J. Control. Release 217, 337–344 (2015).
Anderson, B. R. et al. Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation. Nucleic Acids Res. 38, 5884–5892 (2010).
Bérouti, M. et al. Pseudouridine RNA avoids immune detection through impaired endolysosomal processing and TLR engagement. Cell 188, 4880–4895 (2025).
Cerneckis, J., Cui, Q., He, C., Yi, C. & Shi, Y. Decoding pseudouridine: an emerging target for therapeutic development. Trends Pharmacol. Sci. 43, 522–535 (2022).
Mulroney, T. E. et al. N-Methylpseudouridylation of mRNA causes +1 ribosomal frameshifting. Nature 625, 189–194 (2024).
Svitkin, Y. V. et al. N1-Methyl-pseudouridine in mRNA enhances translation through eIF2α-dependent and independent mechanisms by increasing ribosome density. Nucleic Acids Res. 45, 6023–6036 (2017).
Svitkin, Y. V., Gingras, A.-C. & Sonenberg, N. Membrane-dependent relief of translation elongation arrest on pseudouridine- and N1-methyl-pseudouridine-modified mRNAs. Nucleic Acids Res. 50, 7202–7215 (2022).
Eyler, D. E. et al. Pseudouridinylation of mRNA coding sequences alters translation. Proc. Natl Acad. Sci. USA 116, 23068–23074 (2019).
Monroe, J. et al. N1-Methylpseudouridine and pseudouridine modifications modulate mRNA decoding during translation. Nat. Commun. 15, 8119 (2024).
Baiersdörfer, M. et al. A facile method for the removal of dsRNA contaminant from in vitro-transcribed mRNA. Mol. Ther. Nucleic Acids 15, 26–35 (2019).
Ingolia, N. T., Brar, G. A., Rouskin, S., McGeachy, A. M. & Weissman, J. S. The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments. Nat. Protoc. 7, 1534–1550 (2012).
Leppek, K. et al. Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics. Nat. Commun. 13, 1536 (2022).
Naylor, R., Ho, N. W. & Gilham, P. T. Selective chemical modifications of uridine and pseudouridine in polynucleotides and their effect on the specificities of ribonuclease and phosphodiesterases. J. Am. Chem. Soc. 87, 4209–4210 (1965).
Sidrauski, C., McGeachy, A. M., Ingolia, N. T. & Walter, P. The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly. eLife 4, e05033 (2015).
Karijolich, J. & Yu, Y.-T. Converting nonsense codons into sense codons by targeted pseudouridylation. Nature 474, 395–398 (2011).
Fernández, I. S. et al. Unusual base pairing during the decoding of a stop codon by the ribosome. Nature 500, 107–110 (2013).
Adachi, H. & Yu, Y.-T. Pseudouridine-mediated stop codon readthrough in is sequence context-independent. RNA 26, 1247–1256 (2020).
Ingolia, N. T., Lareau, L. F. & Weissman, J. S. Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell 147, 789–802 (2011).
Rajan, K. S. et al. Structural and mechanistic insights into the function of Leishmania ribosome lacking a single pseudouridine modification. Cell Rep. 43, 114203 (2024).
Cappannini, A. et al. MODOMICS: a database of RNA modifications and related information. 2023 update. Nucleic Acids Res. 52, D239–D244 (2023).
Holm, M. et al. mRNA decoding in human is kinetically and structurally distinct from bacteria. Nature 617, 200–207 (2023).
Milicevic, N., Jenner, L., Myasnikov, A., Yusupov, M. & Yusupova, G. mRNA reading frame maintenance during eukaryotic ribosome translocation. Nature 625, 393–400 (2023).
Demeshkina, N., Jenner, L., Westhof, E., Yusupov, M. & Yusupova, G. A new understanding of the decoding principle on the ribosome. Nature 484, 256–259 (2012).
Davis, D. R. Stabilization of RNA stacking by pseudouridine. Nucleic Acids Res. 23, 5020–5026 (1995).
Kierzek, E. et al. The contribution of pseudouridine to stabilities and structure of RNAs. Nucleic Acids Res. 42, 3492–3501 (2014).
Sokoloski, J. E., Godfrey, S. A., Dombrowski, S. E. & Bevilacqua, P. C. Prevalence of syn nucleobases in the active sites of functional RNAs. RNA 17, 1775–1787 (2011).
Sonenberg, N., Hershey, J. W. B. & Mathews, M. B. Translational Control of Gene Expression (CSHL Press, 2001).
Ingolia, N. T., Hussmann, J. A. & Weissman, J. S. Ribosome profiling: global views of translation. Cold Spring Harb. Perspect. Biol. 11, a032698 (2019).
Zu, T. et al. Metformin inhibits RAN translation through PKR pathway and mitigates disease in ALS/FTD mice. Proc. Natl Acad. Sci. USA 117, 18591–18599 (2020).
Sidrauski, C. et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. eLife 2, e00498 (2013).
Boo, S. H. & Kim, Y. K. The emerging role of RNA modifications in the regulation of mRNA stability. Exp. Mol. Med. 52, 400–408 (2020).
Lewis, C. J. T. et al. Quantitative profiling of human translation initiation reveals elements that potently regulate endogenous and therapeutically modified mRNAs. Mol. Cell https://doi.org/10.1016/j.molcel.2024.11.030 (2024).
von der Haar, T. et al. Translation of in vitro-transcribed RNA therapeutics. Front. Mol. Biosci. 10, 1128067 (2023).
Jiang, Y. et al. Quantitating endosomal escape of a library of polymers for mRNA delivery. Nano Lett. 20, 1117–1123 (2020).
Yanagiya, A. et al. Translational homeostasis via the mRNA cap-binding protein, eIF4E. Mol. Cell 46, 847–858 (2012).
Diamond, P. D., McGlincy, N. J. & Ingolia, N. T. Depletion of cap-binding protein eIF4E dysregulates amino acid metabolic gene expression. Mol. Cell 84, 2119–2134 (2024).
Yanagiya, A. et al. Requirement of RNA binding of mammalian eukaryotic translation initiation factor 4GI (eIF4GI) for efficient interaction of eIF4E with the mRNA cap. Mol. Cell. Biol. 29, 1661–1669 (2009).
Kim, K. Q. et al. N1-methylpseudouridine found within COVID-19 mRNA vaccines produces faithful protein products. Cell Rep. 40, 111300 (2022).
Hia, F. et al. Codon bias confers stability to human mRNAs. EMBO Rep. 20, e48220 (2019).
Plotkin, J. B. & Kudla, G. Synonymous but not the same: the causes and consequences of codon bias. Nat. Rev. Genet. 12, 32–42 (2011).
Erdmann-Pham, D. D., Dao Duc, K. & Song, Y. S. The key parameters that govern translation efficiency. Cell Syst. 10, 183–192 (2020).
Lyons, E. F. et al. Translation elongation as a rate limiting step of protein production. Preprint at bioRxiv https://doi.org/10.1101/2023.11.27.568910 (2024).
Barrington, C. L. et al. Synonymous codon usage regulates translation initiation. Cell Rep. 42, 113413 (2023).
Bonderoff, J. M. & Lloyd, R. E. Time-dependent increase in ribosome processivity. Nucleic Acids Res. 38, 7054–7067 (2010).
Afonina, Z. A., Myasnikov, A. G., Shirokov, V. A., Klaholz, B. P. & Spirin, A. S. Conformation transitions of eukaryotic polyribosomes during multi-round translation. Nucleic Acids Res. 43, 618–628 (2015).
Rajan, K. S. et al. Identification and functional implications of pseudouridine RNA modification on small noncoding RNAs in the mammalian pathogen Trypanosoma brucei. J. Biol. Chem. 298, 102141 (2022).
Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
Mindell, J. A. & Grigorieff, N. Accurate determination of local defocus and specimen tilt in electron microscopy. J. Struct. Biol. 142, 334–347 (2003).
Kucukelbir, A., Sigworth, F. J. & Tagare, H. D. Quantifying the local resolution of cryo-EM density maps. Nat. Methods 11, 63–65 (2014).
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010).
Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82 (2021).
Leonarski, F., Henning-Knechtel, A., Kirmizialtin, S., Ennifar, E. & Auffinger, P. Principles of ion binding to RNA inferred from the analysis of a 1.55 Å resolution bacterial ribosome structure—Part I: Mg2+. Nucleic Acids Res. 53, gkae1148 (2025).
Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D 74, 531–544 (2018).
Williams, C. J. et al. MolProbity: more and better reference data for improved all-atom structure validation. Protein Sci. 27, 293–315 (2018).
Tirosh, O. et al. The transcription and translation landscapes during human cytomegalovirus infection reveal novel host-pathogen interactions. PLoS Pathog. 11, e1005288 (2015).
Erhard, F. et al. Improved Ribo-seq enables identification of cryptic translation events. Nat. Methods 15, 363–366 (2018).
نشر لأول مرة على: www.nature.com
تاريخ النشر: 2026-01-14 02:00:00
الكاتب: Batsheva Rozman
تنويه من موقع “yalebnan.org”:
تم جلب هذا المحتوى بشكل آلي من المصدر:
www.nature.com
بتاريخ: 2026-01-14 02:00:00.
الآراء والمعلومات الواردة في هذا المقال لا تعبر بالضرورة عن رأي موقع “yalebnan.org”، والمسؤولية الكاملة تقع على عاتق المصدر الأصلي.
ملاحظة: قد يتم استخدام الترجمة الآلية في بعض الأحيان لتوفير هذا المحتوى.
