Poster abstracts

Poster number 103 submitted by Darren Parker

Alternative mRNA splicing has a functional role in Mammalian liver development

Amruta Bhate (Biochemistry, University of Illinois, Urbana Champaign), Darren John Parker (Biochemistry, University of Illinois, Urbana Champaign), Anthony Chau, Sandip Chorghade, Auinash Kalsotra (Biochemistry, University of Illinois, Urbana Champaign), Xinshu Xiao, Ahn Jaegyoon (Department of Integrative Biology and Physiology, University of California, Los Angeles)

Abstract:
Liver, the major metabolic organ of the body, undergoes dramatic transitions with regards to structure and function during development. Alternative mRNA splicing (AS) is one of the most prominent mechanisms to generate mRNA complexity, which in turn results in increased proteome diversity. Therefore, we aim to investigate the functional role of AS in mammalian liver development.

To characterize the conserved AS program during liver development, we performed RNA-seq of mouse livers between E18 and P28 timepoints. Among the 150 validated events, 108 (72%) exhibit an increase, and 42 (28%) exhibit a decrease in inclusion of the variably spliced region. Based on this dataset, we performed a temporal analysis of intervening time points, (E16, E18, P0, P2, P7, P14, P28 and P90) and have characterized events that follow prenatal, postnatal and biphasic patterns of splicing. Direct comparison of 118 splicing transitions between mouse and human shows that 57 are evolutionarily conserved during development. Studying these splicing transition networks will be fundamental to understand the regulatory programs that govern development.

We investigated the expression of MBNL1 and CELF1 during liver development and observed that they are strongly down regulated (13 fold and 6 fold respectively) during the first four weeks of liver development. This indicates that changes in splicing factors might play a major role in governing the AS landscape during development. Using knockout and transgenic mice we will further investigate RBPs role in liver development by analyzing the change in splicing patterns due to the absence or presence of these factors. Further studies plan to perform genome-wide iCLIP experiments to determine the direct pre-mRNA targets of these splicing factors.

This study will help us identify conserved mRNA processing transitions in liver development and also establish strong correlations between splicing changes and it’s putative regulators.

Keywords: Alternative Splicing, Liver Development, RNA Binding Proteins