Poster abstracts

Poster number 126 submitted by Rajneesh Srivastava

Structure and constraints imposed on the network of miRNA mediated regulation of RNA-binding proteins in the human genome

Rajneesh Srivastava (Biohealth Informatics, IUPUI), Manjunath (Biohealth Informatics, IUPUI), Sarath Chandra Janga (Biohealth Informatics, IUPUI)

Abstract:
MicroRNAs (miRs) and RNA-binding proteins (RBPs) mediate post transcriptional regulation with uncharacterized communication among themselves on a global scale, thus amplifying a new level of complexity of gene expression and regulation. In this study, we aimed to investigate the miR control over RBPs with respect to non-RBPs, at transcript level and its impact at protein level.
We predicted miR targeted transcripts globally using TargetScan and miRanda and calculated the proportion of target transcripts (separately for RBPs and non-RBPs) controlled by each miRs. Such global miR control were analysed for their impact on (a) targeted transcripts’ expression [Human body map RNA sequence data, quantified by SAILFISH] pattern across 16 tissue type (b) RBPs’ transcript half life [HEK293] and (c) targets’ protein abundance (Human Protein Atlas) pattern across 9 tissue type, using equal binning approach with respect to degree of miR regulation.
We observed that miR regulation over proportion of targeted RBP transcripts and targeted Non RBPs transcripts exihibit varying distribution (p-value < 2.2e-16) and also affirms scale free distribution of miRs over available RBP transcripts with more than 50% of unique RBP transcripts targeted by 0.3% extensively regulating miRs including miR-4739, miR-4728-5p, miR-608, miR-149-3p and ~52% of RBP transcripts targeted by 28% weakly regulating miRs. miRs follows a consistent miRs controlling pattern over RBP (further supported by half lives) as well as non-RBP at transcript level in all tissue types, further justify its involvement in degrading/destabilization. However miRs have no significant influence over RBP protein level when compared to Non-RBPs.
Our study suggests that miRs maintains an equilibrium in between RBP transcript availability and corresponding RBP protein levels through complex uncharacterized buffering mechanism or by checking the frequent translation event of RBP transcript thus allowing “protein synthesis as per need” in cells.

References:
Castello, A.; Horos, R.; Strein, C.; Fischer, B. et al. System-wide identification of rna-binding proteins by interactome capture. Nature protocols 2013, 8, 491-500.

Janga, S.C.; Vallabhaneni, S. Micrornas as post-transcriptional machines and their interplay with cellular networks. Advances in experimental medicine and biology 2011, 722, 59-74.

Hashemikhabir S, Neelamraju Y, Janga SC. Database of RNA binding protein expression and disease dynamics (READ DB). Database (Oxford). 2015, doi: 10.1093/database/bav072.

Neelamraju, Y.; Hashemikhabir, S.; Janga, S.C. The human rbpome: From genes and proteins to human disease. Journal of proteomics 2015.

Kechavarzi, B.; Janga, S.C. Dissecting the expression landscape of rna-binding proteins in human cancers. Genome biology 2014, 15, R14.

Keywords: microRNA, RNA binding proteins, post-transcriptional network