Ultraconserved Nonsense: Pervasive Unproductive Splicing of SR Proteins<br/><br/>Associated with Exceptionally Conserved DNA Elements -- A Bizarre Prevalent Mode of Gene Regulation

Wednesday, October 31, 2007 - 1:45pm - 2:00pm
EE/CS 3-180
Steven Brenner (University of California, Berkeley)
Nonsense-mediated mRNA decay (NMD) is a cellular RNA surveillance system
that recognizes transcripts with premature termination codons and degrades
them. We previously discovered large numbers of natural alternative splice
forms that appear to be targets for NMD, and we speculated that this might
be a mode of gene regulation which we termed RUST (regulated unproductive
splicing and translation). This seems to be confirmed by our finding that
all conserved members of the SR family of splice regulators have an
unproductive alternative mRNA isoform targeted for NMD. Strikingly, the
splice pattern for each is conserved in mouse and always associated with
an ultraconserved or highly-conserved region of ~100 or more nucleotides
of perfect identity between human and mouse. Remarkably, this seems to
have evolved independently in every one of the genes, suggesting that this
is a natural mode of regulation.