Talk on Saturday 03:35-03:55pm submitted by Sarath Chandra Janga
Uncovering the RNA binding protein machinery associated with age and gender during liver development
Praneet Chaturvedi (Bio-Health Informatics, School of Informatics & Computing, Indiana University- Purdue University, Indianapolis), Yaseswini Neelamraju (Bio-Health Informatics, School of Informatics & Computing, Indiana University- Purdue University, Indianapolis), Waqar Arif (Departments of Biochemistry and Medical Biochemistry, University of Illinois, Urbana-Champaign), Auinash Kalsotra (Departments of Biochemistry and Medical Biochemistry, University of Illinois, Urbana-Champaign), Sarath Chandra Janga (Bio-Health Informatics, School of Informatics & Computing, Indiana University- Purdue University, Indianapolis)
Alterations in the expression of genes are known to be associated with changing age and gender although the mechanisms mediating such a change remain unclear. In the present study, we perform an association analysis focusing on the expression changes of 1344 RNA Binding proteins (RBPs) as a function of age and gender in human liver. We identify 88 and 45 RBPs to be significantly associated with age and gender respectively. Majority (~60%) of the age-associated RBPs were found to be increasing in their expression levels with age. Experimental verification of several of the predicted associations in the mouse model confirmed our findings. Our results suggest that a small fraction of the gender-associated RBPs (~40%) are likely to be up-regulated in males. Altogether, these observations state that RBPs are important developmental regulators. Further analysis of the protein interaction network of RBPs associated with age and gender based on the centrality measures like degree, betweenness and closeness revealed that several of these RBPs might be prominent players in liver development and impart gender specific alterations in gene expression via the formation of protein complexes. Indeed, both age and gender-associated RBPs in liver were found to show significantly higher clustering coefficients and network centrality measures compared to non-associated RBPs. Thus, the compendium of RBPs and this study will not only help us gain insight into the role of post-transcriptional regulatory molecules in aging and gender specific expression of genes but also provide a foundation for identifying the regulators contributing to the splicing eQTLs increasingly being discovered in association studies.
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Keywords: Liver Development, Genome-wide Association, Regulatory Proteins