Identification of RBPMS as a mammalian smooth muscle master splicing regulator via proximity of its gene with super-enhancers.
Published version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Abstract
Alternative splicing (AS) programs are primarily controlled by regulatory RNA-binding proteins (RBPs). It has been proposed that a small number of master splicing regulators might control cell-specific splicing networks and that these RBPs could be identified by proximity of their genes to transcriptional super-enhancers. Using this approach we identified RBPMS as a critical splicing regulator in differentiated vascular smooth muscle cells (SMCs). RBPMS is highly down-regulated during phenotypic switching of SMCs from a contractile to a motile and proliferative phenotype and is responsible for 20% of the AS changes during this transition. RBPMS directly regulates AS of numerous components of the actin cytoskeleton and focal adhesion machineries whose activity is critical for SMC function in both phenotypes. RBPMS also regulates splicing of other splicing, post-transcriptional and transcription regulators including the key SMC transcription factor Myocardin, thereby matching many of the criteria of a master regulator of AS in SMCs.
Description
Keywords
Journal Title
Conference Name
Journal ISSN
2050-084X
Volume Title
Publisher
Publisher DOI
Sponsorship
British Heart Foundation (None)
British Heart Foundation (PG/16/28/32123)
Wellcome Trust (209368/Z/17/Z)
Medical Research Council (MC_PC_12009)
British Heart Foundation (FS/18/46/33663)