Poster abstracts
Poster number 122 submitted by Pieter Spealman
Ribosome occupancy of RNA cis-regulatory sequences, uORFs, implicated in the simultaneous regulation of gene expression across two levels.
Pieter Spealman (Department of Biological Sciences, Carnegie Mellon University), Joel McManus (Department of Biological Sciences, Carnegie Mellon University)
Abstract:
It has long been understood that the regulation of gene expression plays a major role in the construction of phenotype from genotype. However, gene regulation has been difficult to study because it is multi-faceted and continuous, involving multiple processes. It has recently become possible to measure regulation at both the transcriptional and translational levels with the advent of ribosome profiling, a deep-sequencing method that allows genome-wide measurement of ribosome occupancy and position on transcripts. Our lab has previously used this approach to identify genes whose regulation has diverged at both levels in two yeast species. One type of this interlevel regulation is 'amplification', where divergence in mRNA abundance is reinforced by post-transcriptional regulation that results in an even greater divergence in ribosome occupancy. Amplified divergence in gene expression may be particularly important for species adaptation. However, the mechanisms responsible for amplifying divergence have yet to be elucidated.
We chose to investigate the mechanisms of divergence using a subset of amplified genes in which both mRNA levels and translation efficiency have evolved reinforcing changes in cis-regulatory sequences (cis-plus-cis genes). By comparing ribosome locations among cis-plus-cis genes, we present evidence suggesting that a single mechanism may be responsible for divergence of both mRNA abundance and translation efficiency. We observed that cis-plus-cis amplified genes are significantly enriched in ribosome-occupied upstream open reading frames (occupied uORFs). Based on our preliminary analysis, cis-plus-cis genes are six times more likely to have occupied uORFs compared to a random gene sample. We propose that evolutionary changes in uORF usage allow for mRNA abundance to be co-regulated with ribosome occupancy by simultaneously modulating mRNA degradation and translation efficiency.
Keywords: regulation of gene expression, uORFs, ribosome profiling