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.