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

Annita Louloupi, Evgenia Ntini, Thomas Conrad, Ulf Andersson Vang Ørom*

*Corresponding author for this work

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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. Louloupi et al. describe an approach to detect m6A RNA methylation on nascent RNA. They find that nascent transcripts are often marked by m6A at splice junctions and in introns. The authors show that m6A at splice junctions contributes to faster splicing, while m6A in introns is associated with alternative splicing.

Original languageEnglish
JournalCell Reports
Volume23
Issue12
Pages (from-to)3429-3437
Number of pages9
ISSN2211-1247
DOIs
Publication statusPublished - 19 Jun 2018

Keywords

  • alternative splicing
  • m6A
  • nascent RNA
  • RNA
  • RNA modifications
  • splicing dynamics

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