Document Detail


Splicing factor SRSF3 is crucial for hepatocyte differentiation and metabolic function.
MedLine Citation:
PMID:  23299886     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
SR family RNA binding proteins regulate splicing of nascent RNAs in vitro but their physiological role in vivo is largely unexplored, as genetic deletion of many SR protein genes results in embryonic lethality. Here we show that SRSF3HKO mice carrying a hepatocyte-specific deletion of Srsf3 (homologous to human SRSF3/SRp20) have a disrupted hepatic architecture and show pre- and postnatal growth retardation. SRSF3HKO mice exhibit impaired hepatocyte maturation with alterations in glucose and lipid homeostasis characterized by reduced glycogen storage, fasting hypoglycemia, increased insulin sensitivity and reduced cholesterol synthesis. We identify various splicing alterations in the SRSF3HKO liver that explain the in vivo phenotype. In particular, loss of SRSF3 causes aberrant splicing of Hnf1α, Ern1, Hmgcs1, Dhcr7 and Scap genes, which are critical regulators of glucose and lipid metabolism. Our study provides the first evidence for a SRSF3-driven genetic programme required for morphological and functional differentiation of hepatocytes that may have relevance for human liver disease and metabolic dysregulation.
Authors:
Supriya Sen; Hassan Jumaa; Nicholas J G Webster
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nature communications     Volume:  4     ISSN:  2041-1723     ISO Abbreviation:  Nat Commun     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-09     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101528555     Medline TA:  Nat Commun     Country:  England    
Other Details:
Languages:  eng     Pagination:  1336     Citation Subset:  IM    
Affiliation:
1] Medical Research Service, VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, California 92161, USA. [2] Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, California 92093, USA.
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