Informace o publikaci

m6A sites in the coding region trigger translation-dependent mRNA decay

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ZHOU You COROVIC Miona HOCH-KRAFT Peter MEISER Nathalie MESITOV Mikhail KOERTEL Nadine BACK Hannah NAARMANN-DE Vries Isabel S KATTI Kritika Suresh OBRDLÍK Aleš BUSCH Anke DIETERICH Christoph VAŇÁČOVÁ Štěpánka HENGESBACH Martin ZARNACK Kathi KOENIG Julian

Rok publikování 2024
Druh Článek v odborném periodiku
Časopis / Zdroj Molecular Cell
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www https://www.sciencedirect.com/science/article/pii/S1097276524008736?via%3Dihub
Doi http://dx.doi.org/10.1016/j.molcel.2024.10.033
Klíčová slova CODON OPTIMALITY; QUALITY-CONTROL; TRANSCRIPTOME; METHYLATION; REVEALS; PURIFICATION; ELONGATION; SELECTION
Přiložené soubory
Popis 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 30 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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