Transient N-6-Methyladenosine Transcriptome Sequencing Reveals a Regulatory Role of m6A in Splicing Efficiency

Cell Rep. 2018 Jun 19;23(12):3429-3437. doi: 10.1016/j.celrep.2018.05.077.

Abstract

Splicing efficiency varies among transcripts, and tight control of splicing kinetics is crucial for coordinated gene expression. N-6-methyladenosine (m6A) is the most abundant RNA modification and is involved in regulation of RNA biogenesis and function. The impact of m6A on regulation of RNA splicing kinetics is unknown. Here, we provide a time-resolved high-resolution assessment of m6A on nascent RNA transcripts and unveil its importance for the control of RNA splicing kinetics. We find that early co-transcriptional m6A deposition near splice junctions promotes fast splicing, while m6A modifications in introns are associated with long, slowly processed introns and alternative splicing events. In conclusion, we show that early m6A deposition specifies the fate of transcripts regarding splicing kinetics and alternative splicing.

Keywords: RNA; RNA modifications; alternative splicing; m6A; nascent RNA; splicing dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Alternative Splicing / genetics*
  • Base Sequence
  • HEK293 Cells
  • Humans
  • Introns / genetics
  • Methyltransferases / genetics
  • RNA / genetics
  • RNA Splicing Factors / metabolism
  • Sequence Analysis, RNA*
  • Transcription, Genetic
  • Transcriptome / genetics*

Substances

  • RNA Splicing Factors
  • RNA
  • N-methyladenosine
  • Methyltransferases
  • METTL3 protein, human
  • Adenosine