Splicing factor SRSF6 promotes hyperplasia of sensitized skin

被引：97

作者：

Jensen, Mads A. ^{[1
]}

Wilkinson, John E. ^{[2
]}

Krainer, Adrian R. ^{[1
]}

机构：

[1] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[2] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2014年 / 21卷 / 02期

关键词：

TENASCIN-C; PYRUVATE-KINASE; HAIR FOLLICLE; STEM-CELLS; EXPRESSION; GENE; CANCER; VARIANTS; SITE; DIFFERENTIATION;

D O I：

10.1038/nsmb.2756

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：189 / +

页数：11

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