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Voyages to map unexplored parts of the epitranscriptomic world

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주제분류생화학

초록

Nascent transcripts are subject to extensive processing, such as 5ʹ capping, splicing, 3ʹ polyadenylation, RNA editing, and RNA modifications. The transcriptome plasticity conferred by these posttranscriptional regulations can alter gene expression, which is a major driver of proteomic diversity. Similar to epigenetic modifications on DNA and histone proteins, RNA is also subject to various chemical modifications, called epitranscriptomic modifications. Since the first chemical modification of RNA was identified approximately 60 years ago, more than 170 RNA modifications have been identified, including N6-methyladenosine (m6A), pseudouridine (Ψ), 2ʹ-O-methylation, (Nm), 5-methylcytidine (m5C), and 8-oxoguanine (o8G). Different RNA species, such as ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), messenger RNAs (mRNAs), and noncoding RNAs (ncRNAs), are frequently posttranscriptionally modified. In particular, studies in the past decade have suggested that these modifications influence almost all aspects of RNA metabolism, including stability, splicing, localization, RNA–protein interaction, and translation1. Indeed, these RNA modifications exhibit essential functions in many biological contexts, including normal development, adult tissue homeostasis, and cancer2,3.

Abstract

Nascent transcripts are subject to extensive processing, such as 5ʹ capping, splicing, 3ʹ polyadenylation, RNA editing, and RNA modifications. The transcriptome plasticity conferred by these posttranscriptional regulations can alter gene expression, which is a major driver of proteomic diversity. Similar to epigenetic modifications on DNA and histone proteins, RNA is also subject to various chemical modifications, called epitranscriptomic modifications. Since the first chemical modification of RNA was identified approximately 60 years ago, more than 170 RNA modifications have been identified, including N6-methyladenosine (m6A), pseudouridine (Ψ), 2ʹ-O-methylation, (Nm), 5-methylcytidine (m5C), and 8-oxoguanine (o8G). Different RNA species, such as ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), messenger RNAs (mRNAs), and noncoding RNAs (ncRNAs), are frequently posttranscriptionally modified. In particular, studies in the past decade have suggested that these modifications influence almost all aspects of RNA metabolism, including stability, splicing, localization, RNA–protein interaction, and translation1. Indeed, these RNA modifications exhibit essential functions in many biological contexts, including normal development, adult tissue homeostasis, and cancer2,3.

참고문헌 (11)

  1. Zhao, B. S., "Post-transcriptional gene regulation by mRNA modifications", Nat. Rev. Mol. Cell Biol, 18, pp.31~42 (2017)
  2. Gu, C., "RNA m(6)A modification in cancers: molecular mechanisms and potential clinical applications", Innov. (Camb.), 1, pp.100066~ (2020)
  3. Chan-Woo Park, "Epitranscriptomic regulation of transcriptome plasticity in development and diseases of the brain", BMB Reports, 53(11), pp.551~564 (2020), 생화학분자생물학회[DOI]
  4. Zhang Yanling, "Detection technologies for RNA modifications", Experimental and Molecular Medicine, 54, pp.1~16 (2022), 생화학분자생물학회[DOI]
  5. Liu, J., "The RNA m(6)A reader YTHDC1 silences retrotransposons and guards ES cell identity", Nature, 591, pp.322~326 (2021)
  6. Xu, W., "METTL3 regulates heterochromatin in mouse embryonic stem cells", Nature, 591, pp.317~321 (2021)
  7. Geula, S., "Stem cells. m6A mRNA methylation facilitates resolution of naive pluripotency toward differentiation", Science, 347, pp.1002~1006 (2015)
  8. 채영현, "New insights into the epitranscriptomic control of pluripotent stem cell fate", Experimental and Molecular Medicine, 54, pp.1~9 (2022), 생화학분자생물학회[DOI]
  9. Turkalj Elena M., "The emerging importance of METTL5-mediated ribosomal RNA methylation", Experimental and Molecular Medicine, 54, pp.1~9 (2022), 생화학분자생물학회[DOI]
  10. Seok, H., "Position-specific oxidation of miR-1 encodes cardiac hypertrophy", Nature, 584, pp.279~285 (2020)
  11. Hahm Ja Young, "8-Oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification", Experimental and Molecular Medicine, 54, pp.1~17 (2022), 생화학분자생물학회[DOI]

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