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Intron retention is regulated by altered MeCP2-mediated splicing factor recruitment.

Authors :
Wong, Justin J. -L.
Gao, Dadi
Nguyen, Trung V.
Kwok, Chau-To
van Geldermalsen, Michelle
Middleton, Rob
Pinello, Natalia
Thoeng, Annora
Nagarajah, Rajini
Holst, Jeff
Ritchie, William
Rasko, John E. J.
Source :
Nature Communications; May2017, Vol. 8 Issue 5, p15134, 1p
Publication Year :
2017

Abstract

While intron retention (IR) is considered a widely conserved and distinct mechanism of gene expression control, its regulation is poorly understood. Here we show that DNA methylation directly regulates IR. We also find reduced occupancy of MeCP2 near the splice junctions of retained introns, mirroring the reduced DNA methylation at these sites. Accordingly, MeCP2 depletion in tissues and cells enhances IR. By analysing the MeCP2 interactome using mass spectrometry and RNA co-precipitation, we demonstrate that decreased MeCP2 binding near splice junctions facilitates IR via reduced recruitment of splicing factors, including Tra2b, and increased RNA polymerase II stalling. These results suggest an association between IR and a slower rate of transcription elongation, which reflects inefficient splicing factor recruitment. In summary, our results reinforce the interdependency between alternative splicing involving IR and epigenetic controls of gene expression. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20411723
Volume :
8
Issue :
5
Database :
Complementary Index
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
123379446
Full Text :
https://doi.org/10.1038/ncomms15134