Splicing factor SRSF6 promotes hyperplasia of sensitized skin

Jensen, M. A., Wilkinson, J. E., Krainer, A. R. (January 2014) Splicing factor SRSF6 promotes hyperplasia of sensitized skin. Nature Structural and Molecular Biology, 21. pp. 189-197. ISSN 15459993 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/24440982

DOI: 10.1038/nsmb.2756

Abstract

Many biological processes involve gene-expression regulation by alternative splicing. Here, we identify the splicing factor SRSF6 as a regulator of wound healing and tissue homeostasis in skin. We show that SRSF6 is a proto-oncogene frequently overexpressed in human skin cancer. Overexpressing it in transgenic mice induces hyperplasia of sensitized skin and promotes aberrant alternative splicing. We identify 139 SRSF6-target genes in skin and show that this SR-rich protein binds to alternative exons in the pre-mRNA of the extracellular-matrix protein tenascin C, thus promoting the expression of isoforms characteristic of invasive and metastatic cancer independently of cell type. SRSF6 overexpression additionally results in depletion of LGR6+ stem cells and excessive keratinocyte proliferation and response to injury. Furthermore, the effects of SRSF6 in wound healing assayed in vitro depend on the tenascin-C isoforms. Thus, abnormal SR-protein expression can perturb tissue homeostasis.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organs, tissues, organelles, cell types and functions > organs types and functions > skin bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > splicing factor
CSHL Authors:	Jensen, Mads Aaboe Krainer, Adrian R.
Communities:	CSHL Cancer Center Program > Gene Regulation and Cell Proliferation CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > Animal Tissue and Imaging Service CSHL Cancer Center Shared Resources > Antibody and Phage Display Service CSHL Cancer Center Shared Resources > Flow Cytometry Service CSHL Cancer Center Shared Resources > Functional Genomics and Genetics Service CSHL Cancer Center Shared Resources > Gene Targeting Service CSHL Cancer Center Shared Resources > Genetic Screening Service CSHL Cancer Center Shared Resources > Histology Service CSHL Cancer Center Shared Resources > Microscopy Service CSHL Cancer Center Shared Resources > Next Generation Sequencing Service CSHL labs > Krainer lab CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User:	Matt Covey
Date:	January 2014
Date Deposited:	07 Feb 2014 21:38
Last Modified:	04 Nov 2015 20:18
PMCID:	PMC4118672
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/29491

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