Talk abstracts
Talk on Friday 01:15-01:30pm submitted by Noah Helton
Ribosome association excludes stress-induced gene mRNAs from stress granules
Noah Helton (Department of Human Genetics, University of Michigan ), Ben Dodd (Department of Human Genetics, University of Michigan ), Stephanie Moon (Department of Human Genetics, University of Michigan )
Abstract:
The integrated stress response (ISR) is critical for resilience to stress and is implicated in numerous diseases. During the ISR, translation is repressed, stress-induced genes are expressed, and mRNAs condense into stress granules. The
relationship between stress granules and stress-induced gene expression is unclear. We measured endogenous stress-induced gene mRNA localization at the single-molecule level in the presence or absence of small molecule translation inhibitors. Reducing ribosome association increases the localization of stress-induced gene mRNAs to stress granules, whereas increasing ribosome association inhibits their localization to stress granules. The presence of
upstream open reading frames (uORFs) in mRNA reporters reduces their localization to stress granules in a ribosome-dependent manner. Furthermore, a single initiating ribosome blocks stress granule formation and inhibits
mRNA association with preformed stress granules. Thus, uORF-mediated ribosome association inhibits stress-induced gene mRNA localization to stress granules, suggesting a new role for uORFs in limiting RNA condensation. We are further pursuing mechanisms of how a single ribosome can be sufficient to inhibit stress granule assembly, and how uORFs could be leveraged in other instances to inhibit mRNA condensation.
Keywords: Translation, Stress Granules, uORFs