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quarta-feira, junho 20, 2018

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

Annita Louloupi5, Evgenia Ntini5, Thomas Conrad, Ulf Andersson Vang Ørom6

5These authors contributed equally

6Lead Contact

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DOI: https://doi.org/10.1016/j.celrep.2018.05.077 |

Article Info

Publication History

Published: June 19, 2018 Accepted: May 23, 2018

Received in revised form: April 30, 2018 Received: January 10, 2018

User License

Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)

Source/Fonte: Ulf Andersson Vang Ørom 

Highlights

•A time-resolved high-resolution picture of m6A on nascent RNA transcripts

•m6A is deposited at nascent RNA and in introns

•m6A deposition at splice-junctions increases splicing kinetics

•High m6A levels in introns is associated with slow and alternative splicing

Summary

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.

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