Talk abstracts
Talk on Friday 01:15-01:30pm submitted by Amruta Bhate
ESRP2 controls an adult splicing program in hepatocytes to support postnatal liver maturation
Amruta Bhate (Department of Biochemistry and Medical Biochemistry, University of Illinois, Urbana Champaign), Darren J. Parker (Department of Biochemistry and Medical Biochemistry, University of Illinois, Urbana Champaign), Thomas W. Bebee (Departments of Medicine and Genetics, Perelman School of Medicine, University of Pennsylvania), Jaegyoon Ahn (Department of Integrative Biology and Physiology, University of California, Los Angeles), Russ P. Carstens (Departments of Medicine and Genetics, Perelman School of Medicine, University of Pennsylvania), Auinash Kalsotra (Department of Biochemistry and Medical Biochemistry, University of Illinois, Urbana Champaign)
Abstract:
Although major genetic networks controlling early liver specification and morphogenesis are known, the mechanisms responsible for postnatal hepatic maturation are poorly understood. Here we employ global analyses of the mouse liver transcriptome to demonstrate that postnatal remodeling of the liver is accompanied by large-scale transcriptional and post-transcriptional transitions that are cell-type-specific and temporally coordinated. Combining detailed expression analyses with gain- and loss-of-function studies, we identify Epithelial Splicing Regulatory Protein 2 (ESRP2) as a conserved regulatory factor that controls the postnatal switch of approximately 20% of splice isoforms in mouse and human hepatocytes. The normal shift in splicing coincides tightly with dramatic postnatal induction of ESRP2 in hepatocytes such that deletion of Esrp2 in mice results in failure of neonatal-to-adult splicing transitions in a spectrum of genes involved in cell proliferation, differentiation and adhesion. We further demonstrate that forced expression of ESRP2 in immature mouse and human hepatocytes is sufficient to drive a reciprocal shift in splicing. Phenotypic and biochemical characterization of Esrp2 null mice reveals defects in cell proliferation, hepatic zonation abnormalities, and reduction in albumin production. Taken together, these findings define a direct role for ESRP2 in the generation of conserved repertoires of adult splice isoforms that facilitate postnatal liver growth and maturation.
References:
Bhate, A; Parker, D et al. 'ESRP2 Controls an Adult Splicing Program in Hepatocytes to Support Postnatal Liver Maturation' Nature Communications (in press)
Keywords: Alternative splicing, ESRP2, liver maturation