Location: Fields Institute , 222 College Street, Toronto

January 22, 2010- 3:30 p.m.
Dr. Quaid Morris
University of Toronto

Predicting the targets of mRNA-binding proteins

RNA-binding domains are among the most common domains in eukaryotic genomes and RNA-binding proteins (RBPs) play critical roles in post-transcriptional regulation (PTR) of gene expression by regulating mRNA processing, mRNA translation, mRNA export and mRNA stability. However, despite their importance, little is known about how RBPs identify their target sites.

As a first step towards building quantitative models of PTR, we are mapping out mRNA and RBP interactions using a combined biochemical and computational strategy. Our strategy is based on a microarray-based assay, called RNAcompete, that measures the binding affinity of a recombinant RBP for hundreds of thousands of short RNA sequences. These sequences are designed to comprehensively query the space of possible binding preferences. We use a new RNA motif finding algorithm, RNAcontext, to infer sequence and structural binding preferences of RBPs from the RNAcompete data. However, using these motif models to find RBP binding sites on mRNAs requires estimating mRNA secondary structure computationally. Some of our recent work suggests that estimating this structure is easier than expected.

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