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Review
. 2016 Apr;6(4):160003.
doi: 10.1098/rsob.160003. Epub 2016 Apr 13.

Recent advances in dynamic m6A RNA modification

Guangchao Cao  1 , Hua-Bing Li  2 , Zhinan Yin  3 , Richard A Flavell  4
Affiliations
Review

Recent advances in dynamic m6A RNA modification

Guangchao Cao et al. Open Biol. 2016 Apr.

Abstract

The identification of m(6)A demethylases and high-throughput sequencing analysis of methylated transcriptome corroborated m(6)A RNA epigenetic modification as a dynamic regulation process, and reignited its investigation in the past few years. Many basic concepts of cytogenetics have been revolutionized by the growing understanding of the fundamental role of m(6)A in RNA splicing, degradation and translation. In this review, we summarize typical features of methylated transcriptome in mammals, and highlight the 'writers', 'erasers' and 'readers' of m(6)A RNA modification. Moreover, we emphasize recent advances of biological functions of m(6)A and conceive the possible roles of m(6)A in the regulation of immune response and related diseases.

Keywords: m6A; mRNA; methylation.

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Figures

Figure 1.
Figure 1.
Dynamic m6A RNA modifications and mediated functions. m6A mRNA methylation is mediated by a multiprotein complex that includes METTL3, METTL14 and WTAP, whereas demethylases, such as FTO and ALKBH5, erase m6A. Recognition of m6A by HNRNPC in the nucleus mediates alternative splicing of pre-mRNA, and HNRNPA2B1 promotes pri-miRNA processing to pre-miRNA. In cytoplasm, binding of m6A sites with different readers mediates divergent functions. YTHDF1 binds m6A-modified mRNAs through interactions with initiation factors and ribosomes to increase translational output, and eIF3 can also directly bind to 5′UTR m6A to initiate translation, whereas m6A recognition by YTHDF2 leads to mRNA decay. More nuclear and cytoplasmic readers need to be defined to illuminate the functions of m6A in mRNA export, translation and storage.
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