The detection and functions of RNA modification m6A based on m6A writers and erasers

J Biol Chem. 2021 Aug;297(2):100973. doi: 10.1016/j.jbc.2021.100973. Epub 2021 Jul 16.

Abstract

N6-methyladenosine (m6A) is the most frequent chemical modification in eukaryotic mRNA and is known to participate in a variety of physiological processes, including cancer progression and viral infection. The reversible and dynamic m6A modification is installed by m6A methyltransferase (writer) enzymes and erased by m6A demethylase (eraser) enzymes. m6A modification recognized by m6A binding proteins (readers) regulates RNA processing and metabolism, leading to downstream biological effects such as promotion of stability and translation or increased degradation. The m6A writers and erasers determine the abundance of m6A modifications and play decisive roles in its distribution and function. In this review, we focused on m6A writers and erasers and present an overview on their known functions and enzymatic molecular mechanisms, showing how they recognize substrates and install or remove m6A modifications. We also summarize the current applications of m6A writers and erasers for m6A detection and highlight the merits and drawbacks of these available methods. Lastly, we describe the biological functions of m6A in cancers and viral infection based on research of m6A writers and erasers and introduce new assays for m6A functionality via programmable m6A editing tools.

Keywords: N(6)-methyladenosine (m(6)A); RNA modification; cancer progression; erasers; m(6)A detection; m(6)A editing; viral infection; writers.

Publication types

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

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Adenosine / genetics
  • Adenosine / metabolism
  • Eukaryotic Cells / metabolism*
  • Humans
  • Methyltransferases / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • RNA Processing, Post-Transcriptional / genetics*
  • RNA, Messenger / genetics*

Substances

  • RNA, Messenger
  • N-methyladenosine
  • 6-methyladenine mRNA methyltransferase
  • Methyltransferases
  • Adenosine