Published on None in volume None.

PubMed ID: 25412661

DOI: 10.1038/cr.2014.152

Abstract:

N6-methyladenosine (m6A) has been demonstrated to be ubiquitous in several types of eukaryotic RNAs, including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), long non-coding RNA (lncRNA), and small nuclear RNA (snRNA)1. The recent discoveries of RNA m6A methyltransferase complex METTL3/METTL14/WTAP and demethylases FTO and ALKBH5 prove the reversibility of m6A modification2,3,4,5,6. This modification plays important roles in various biological processes, including circadian rhythms7, RNA splicing8, yeast meiosis9, and embryonic stem cell self-renewal10. Two recent studies show that YTH domain family 2 (YTHDF2) and other YTHDF proteins preferentially bind to m6A-containing mRNA in vivo and in vitro and regulate localization and stability of the bound mRNA8,11. YTHDF2 is also known to be involved in development of acute myeloid leukemia12. YTHDC1 (splicing factor YT521-B), another YTH domain-containing protein, is known to play an important role in Emery-Dreifuss muscular dystrophy. While the function of YTHDF2 in the regulation of mRNA stability has been explored, the molecular mechanism for specific recognition of m6A by the YTH domain remains elusive.