Modeling the combined effect of RNA-binding proteins and micrornas in post-transcriptional regulation

Thesis Type: Postgraduate

Institution Of The Thesis: Orta Doğu Teknik Üniversitesi, Graduate School of Informatics, Medical Informatics, Turkey

Approval Date: 2015




Post-transcriptional regulation (PTR) controls the gene expression between transcription and translation. Regulation at this level is carried out by the interactions of trans-acting RNA-binding proteins (RBPs) and microRNAs (miRNAs) with cis-regulatory elements in mRNA. Majority of previous work have focused on the effect of a single factor independent of other co-factors bound to the same mRNA. However, recent studies have shown that RBPs and miRNAs can act in cooperation or competition with each other. In this thesis, we mapped the binding sites of both RBPs and miRNAs on human 3’UTRs, and utilized this collection of binding sites to better understand PTR networks. We first focused on several RBPs and assessed how accessibility and conservation differ between experimentally supported sites and other sites that are only computationally predicted. We then investigated the competitive effects of other factors on HuR binding and the resulting transcript abundance change upon HuR depletion. Next, we characterized the potential interactions between the factors by finding those pairs of factors with co-occurrence of motifs higher than expected by chance. Our results show that PUM1 and PUM2 have potential cooperative interactions with miRNAs. Finally, we used logistic regression with features compiled from the counts of sites of factors and dinucleotide frequency to accurately predict the stability and steady-state abundance of mRNAs. Altogether, results of this thesis suggest that studies of PTR must consider the effect of both RBPs and miRNAs, and their interactions.