Mechanistic insights into m6A RNA enzymes

Biochim Biophys Acta Gene Regul Mech. 2019 Mar;1862(3):222-229. doi: 10.1016/j.bbagrm.2018.10.014. Epub 2018 Nov 3.

Abstract

The field of RNA modifications, so-called epitranscriptomics, has flourished over the past years owing to improvements of detection methods and the identification of important regulatory players. N6-methyladenosine (m6A) is the most abundant internal modification in messenger (mRNA) and long non-coding (lncRNA), and controls most steps of RNA metabolism. Its physiological roles range from gametogenesis, stem cell differentiation to immunity, neuronal development and functions, while its alterations are associated with cancer development and progression. In this review we focus on the proteins that catalyze formation of m6A (also called writers) on RNA. Interestingly, distinct proteins deposit m6A on different classes of RNA, indicating that specific RNA features dictate recognition mechanisms. Associated factors and post-translational modifications can also alter m6A enzyme activity. A better understanding of the underlying regulation involved in m6A deposition is the first step towards developing tools for cancer therapy and for treatment of other m6A-associated diseases.

Keywords: MAC; MACOM; Mettl16; Mettl3; RNA modifications; RlmJ; m(6)A.

Publication types

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

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Adenosine / metabolism
  • Animals
  • Catalytic Domain
  • Gene Expression Regulation, Developmental
  • Humans
  • Methyltransferases / chemistry*
  • Methyltransferases / metabolism
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism*

Substances

  • RNA, Messenger
  • N-methyladenosine
  • Methyltransferases
  • Adenosine