Poster abstracts
Poster number 19 submitted by Jackie Chen
Temporally controlled expression of ESRP2 licenses fetal-to-adult switch in alternative splicing required for hepatocyte maturation
Sushant Bangru (Department of Biochemistry, University of Illinois at Urbana-Champaign), Jackie Chen (Department of Biochemistry, University of Illinois at Urbana-Champaign), Auinash Kalsotra (Department of Biochemistry, College of Medicine, Carl R. Woese Institute of Genomic Biology, University of Illinois at Urbana-Champaign)
Abstract:
Postnatal period of development is critical for mammalian tissues and is coordinated through precise activation of genetic programs that govern differentiation, growth and maturation of individual cell lineages. Here, we describe a cell type- and developmental stage-specific program of alternative splicing that drives sequential replacement of fetal-to-adult protein isoforms in the mouse liver. Deep transcriptome analysis of purified fetal and adult mouse hepatocytes coupled with RNA-binding motif enrichment analysis identified Epithelial Splicing regulatory protein 2 (ESRP2) as the major regulator for these developmental splicing decisions. Targeted deletion of ESRP2 in mice resulted in the failure of fetal-to-adult switch in splicing for hundreds of RNA transcripts that encode proteins involved in terminal differentiation and functional competence of hepatocytes. To delineate its exact role in activation of adult splicing program, we generated transgenic mice with tetracycline-inducible and hepatocyte-specific expression of ESRP2. Remarkably, premature expression of ESRP2 in the livers of newborn pups forced an earlier-than-normal onset of adult splicing program. Collectively, these findings highlight the essentiality and temporal requirement for ESRP2 in allowing fetal-to-adult splicing transitions within maturing hepatocytes and broaden our understanding of regulatory mechanisms needed for postnatal liver development and maturation.
Keywords: Liver, splicing, development