m 6 A in mRNA coding regions promotes translation via the RNA helicase-containing YTHDC2
TLDR
It is demonstrated that the m6A reader YTHDC2 — which contains an RNA helicase domain — acts on the coding region to promotes mRNA translation by resolving secondary structures, and established the physiological significance of CDS methylation and uncovered non-overlapping function of m 6A reader proteins.Abstract:
Dynamic mRNA modification in the form of N6-methyladenosine (m6A) adds considerable richness and sophistication to gene regulation. The m6A mark is asymmetrically distributed along mature mRNAs, with approximately 35% of m6A residues located within the coding region (CDS). It has been suggested that methylation in CDS slows down translation elongation. However, neither the decoding feature of endogenous mRNAs nor the physiological significance of CDS m6A has been clearly defined. Here, we found that CDS m6A leads to ribosome pausing in a codon-specific manner. Unexpectedly, removing CDS m6A from these transcripts results in a further decrease of translation. A systemic analysis of RNA structural datasets revealed that CDS m6A positively regulates translation by resolving mRNA secondary structures. We further demonstrate that the elongation-promoting effect of CDS methylation requires the RNA helicase-containing m6A reader YTHDC2. Our findings established the physiological significance of CDS methylation and uncovered non-overlapping function of m6A reader proteins.read more
Citations
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m 6 A RNA methylation: from mechanisms to therapeutic potential
TL;DR: The role of m6-methyladenosine (m6 A) in post-transcriptional gene expression regulation is discussed in this article, where the authors highlight advances in the understanding of the m6 A deposition on mRNA and its context-dependent effects on mRNA decay and translation.
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Roles of METTL3 in cancer: mechanisms and therapeutic targeting
TL;DR: The well-documented protein structure of the METTL3/METTL14 heterodimer provides the basis for potential therapeutic targeting, which is discussed in this review.
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The emerging roles of N6-methyladenosine (m6A) deregulation in liver carcinogenesis
Mengnuo Chen,Chun-Ming Wong +1 more
TL;DR: Deregulation of m6A modification has been recently implicated in human carcinogenesis, including liver cancer, and the potential of exploiting m 6A modification for cancer diagnosis and therapeutics is discussed.
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m6A-binding proteins: the emerging crucial performers in epigenetics.
TL;DR: The specific functions and underlying mechanisms of m6A-binding proteins in tumorigenesis, hematopoiesis, virus replication, immune response,immune response, and adipogenesis are summarized.
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N6-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification
TL;DR: It is demonstrated that METTL3 enhanced the HK2 stability through YTHDF1-mediated m6A modification, thereby promoting the Warburg effect of CC, which might promote a novel insight for the CC treatment.
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