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

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 the regulation of RNA splicing kinetics has not been investigated. Here, we provide the first time-resolved high-resolution assessment of m6A on nascent RNA transcripts and unveil its importance for the control of RNA splicing kinetics. We identify that early co-transcriptional m6A deposition near splice junctions promotes fast splicing, while m6A modification of introns is associated with long, slowly processed introns and alternative splicing events. In conclusion, by directly comparing the processing dynamics of individual transcripts in the methylated versus unmethylated state on a transcriptome-wide scale we show that early m6A deposition marks transcripts for a fast-track processing.