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Elife. 2018 Jan 2;7. pii: e29494. doi: 10.7554/eLife.29494.

Alternative RNA splicing in the endothelium mediated in part by Rbfox2 regulates the arterial response to low flow.

Author information

1
Koch Institute for Integrative Cancer Research, MIT, Cambridge, United States.
2
Department of Biology, MIT, Cambridge, United States.
3
Howard Hughes Medical Institute, United States.
4
Center for Vascular Biology, UCONN Health, Farmington, United States.

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.

KEYWORDS:

Atherosclerosis; alternative splicing; artery; cell biology; endothelial; mouse; platelet; vascular

PMID:
29293084
PMCID:
PMC5771670
DOI:
10.7554/eLife.29494
[Indexed for MEDLINE]
Free PMC Article

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