Alternative RNA splicing in the endothelium mediated in part by Rbfox2 regulates the arterial response to low flow
Name
elife-29494-v2.pdf
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2.17 MB
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Adobe PDF
Checksum (MD5)
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Author(s)
Kimble, Amy L.
Murphy, Patrick A.
Butty, Vincent L. G.
Boutz, Paul
Begum, Shahinoor
Sharp, Phillip A.
Burge, Christopher B.
Hynes, Richard O.
Date Issued
January 2018
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
Murphy, Patrick A, Vincent L Butty, Paul L Boutz, Shahinoor Begum, Amy L Kimble, Phillip A Sharp, Christopher B Burge, and Richard O Hynes. “Alternative RNA Splicing in the Endothelium Mediated in Part by Rbfox2 Regulates the Arterial Response to Low Flow.” eLife 7 (January 2018) © Murphy et al
Version
Final published version
Abstract
Low and disturbed blood flow drives the progression of arterial diseases including atherosclerosis and aneurysms. The endothelial response to flow and its interactions with recruited platelets and leukocytes determine disease progression. Here, we report widespread changes in alternative splicing of pre-mRNA in the flow-activated murine arterial endothelium in vivo. Alternative splicing was suppressed by depletion of platelets and macrophages recruited to the arterial endothelium under low and disturbed flow. Binding motifs for the Rbfox-family are enriched adjacent to many of the regulated exons. Endothelial deletion of Rbfox2, the only family member expressed in arterial endothelium, suppresses a subset of the changes in transcription and RNA splicing induced by low flow. Our data reveal an alternative splicing program activated by Rbfox2 in the endothelium on recruitment of platelets and macrophages and demonstrate its relevance in transcriptional responses during flow-driven vascular inflammation.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Attribution 4.0 International (CC BY 4.0)
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DOI of Published Version
https://doi.org/10.7554/eLife.29494
