Affiliation:
1. Department of Biochemistry, University of Oxford, Oxford OX1 3QU, U.K.
Abstract
The RNA modification N6-methyladenosine (m6A) is conserved across eukaryotes, and profoundly influences RNA metabolism, including regulating RNA stability. METTL3 and METTL14, together with several accessory components, form a ‘writer’ complex catalysing m6A modification. Conversely, FTO and ALKBH5 function as demethylases, rendering m6A dynamic. Key to understanding the functional significance of m6A is its ‘reader' proteins, exemplified by YTH-domain-containing proteins (YTHDFs) canonical reader and insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) non-canonical reader. These proteins play a crucial role in determining RNA stability: YTHDFs mainly promote mRNA degradation through different cytoplasmic pathways, whereas IGF2BPs function to maintain mRNA stability. Additionally, YTHDC1 functions within the nucleus to degrade or protect certain m6A-containing RNAs, and other non-canonical readers also contribute to RNA stability regulation. Notably, m6A regulates retrotransposon LINE1 RNA stability and/or transcription via multiple mechanisms. However, conflicting observations underscore the complexities underlying m6A's regulation of RNA stability depending upon the RNA sequence/structure context, developmental stage, and/or cellular environment. Understanding the interplay between m6A and other RNA regulatory elements is pivotal in deciphering the multifaceted roles m6A plays in RNA stability regulation and broader cellular biology.
Cited by
1 articles.
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