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m6A sites in the coding region trigger translation-dependent mRNA decay
Y. Zhou, M. Ćorović, P. Hoch-Kraft, N. Meiser, M. Mesitov, N. Körtel, H. Back, IS. Naarmann-de Vries, K. Katti, A. Obrdlík, A. Busch, C. Dieterich, Š. Vaňáčová, M. Hengesbach, K. Zarnack, J. König
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
NLK
Cell Press Free Archives
od 1997-12-01 do Před 1 rokem
Free Medical Journals
od 1997 do Před 1 rokem
Free Medical Journals
od 1997 do Před 1 rokem
Open Access Digital Library
od 1997-12-01
- MeSH
- 3' nepřekládaná oblast MeSH
- adenosin * analogy a deriváty metabolismus genetika MeSH
- HEK293 buňky MeSH
- HeLa buňky MeSH
- lidé MeSH
- messenger RNA * genetika metabolismus MeSH
- otevřené čtecí rámce * MeSH
- proteiny vázající RNA * genetika metabolismus MeSH
- proteosyntéza * MeSH
- ribozomy metabolismus genetika MeSH
- stabilita RNA * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
N6-Methyladenosine (m6A) is the predominant internal RNA modification in eukaryotic messenger RNAs (mRNAs) and plays a crucial role in mRNA stability. Here, using human cells, we reveal that m6A sites in the coding sequence (CDS) trigger CDS-m6A decay (CMD), a pathway that is distinct from previously reported m6A-dependent degradation mechanisms. Importantly, CDS m6A sites act considerably faster and more efficiently than those in the 3' untranslated region, which to date have been considered the main effectors. Mechanistically, CMD depends on translation, whereby m6A deposition in the CDS triggers ribosome pausing and transcript destabilization. The subsequent decay involves the translocation of the CMD target transcripts to processing bodies (P-bodies) and recruitment of the m6A reader protein YT521-B homology domain family protein 2 (YTHDF2). Our findings highlight CMD as a previously unknown pathway, which is particularly important for controlling the expression of developmental regulators and retrogenes.
German Centre for Cardiovascular Research Partner Site Heidelberg Mannheim Heidelberg Germany
Institute of Molecular Biology 55128 Mainz Germany
Theodor Boveri Institute Biocenter University of Würzburg Am Hubland 97074 Würzburg Germany
Citace poskytuje Crossref.org
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- $a N6-Methyladenosine (m6A) is the predominant internal RNA modification in eukaryotic messenger RNAs (mRNAs) and plays a crucial role in mRNA stability. Here, using human cells, we reveal that m6A sites in the coding sequence (CDS) trigger CDS-m6A decay (CMD), a pathway that is distinct from previously reported m6A-dependent degradation mechanisms. Importantly, CDS m6A sites act considerably faster and more efficiently than those in the 3' untranslated region, which to date have been considered the main effectors. Mechanistically, CMD depends on translation, whereby m6A deposition in the CDS triggers ribosome pausing and transcript destabilization. The subsequent decay involves the translocation of the CMD target transcripts to processing bodies (P-bodies) and recruitment of the m6A reader protein YT521-B homology domain family protein 2 (YTHDF2). Our findings highlight CMD as a previously unknown pathway, which is particularly important for controlling the expression of developmental regulators and retrogenes.
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