N6-methyladenosine modifications: interactions with novel RNA-binding proteins and roles in signal transduction

RNA Biol. 2019 Aug;16(8):991-1000. doi: 10.1080/15476286.2019.1620060. Epub 2019 May 26.

Abstract

RNA epigenetics has received a great deal of attention in recent years, and the reversible N6-methyladenosine (m6A) modification on messenger RNAs (mRNAs) has emerged as a widespread phenomenon. The vital roles of m6A in diverse biological processes are dependent on many RNA-binding proteins (RBPs) with 'reader' or 'nonreader' functions. Moreover, m6A effector proteins affect cellular processes, such as stem cell differentiation, tumor development and the immune response by controlling signal transduction. This review provides an overview of the interactions of m6A with various RBPs, including the 'reader' proteins (excluding the YT521-B homology (YTH) domain proteins and the heterogeneous nuclear ribonucleoproteins (hnRNPs)), and the functional 'nonreader' proteins, and this review focuses on their specific RNA-binding domains and their associations with other m6A effectors. Furthermore, we summarize key m6A-marked targets in distinct signaling pathways, leading to a better understanding of the cellular m6A machinery.

Keywords: M6a reader; RNA-binding protein; protein domain; signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / genetics
  • Epigenomics*
  • Humans
  • RNA, Messenger / genetics*
  • RNA-Binding Proteins / genetics*
  • Signal Transduction / genetics

Substances

  • RNA, Messenger
  • RNA-Binding Proteins
  • N-methyladenosine
  • Adenosine

Grants and funding

This work was supported by the National Natural Science Foundation, China [grant number 81672362];National Natural Science Foundation of China [81672362].