Poster abstracts
Poster number 5 submitted by Noah Helton
Temporal Gating Dictates Stress-induced Transcript Export From the Nucleus
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:
Prior work has largely focused on transcriptional and translational control during stress, yet how nuclear mRNA export contributes to the stress response is poorly understood. We found that global nuclear mRNA export is progressively inhibited during arsenite and heat stress in human cells. In contrast to prior work conducted predominantly in yeast that suggests stress-induced mRNA export is prioritized through sequence-specific mechanisms, we observed that mRNA export is governed by a temporal gating mechanism, in which the timing of mRNA biogenesis dictates the nucleocytoplasmic distribution of transcripts during stress. Using single-molecule imaging of stress-induced mRNAs and transcriptome-wide sequencing, we observe that most stress-induced transcripts, including heat shock protein mRNAs, accumulate in the nucleus during stress. Only a small subset of stress-induced mRNAs, such as HMOX1, JUN, and FOS, avoid nuclear accumulation. We also discovered that mRNAs transcribed early during stress, including those encoding immediate early genes, redox mediators, and a subset of protein chaperones, are exported from the nucleus before the global inhibition of mRNA export. In contrast, mRNAs transcribed later are retained in the nucleus until stress is resolved. Reporter RNA assays confirm that transcriptional timing determines mRNA export competence. This work reveals that the timing of mRNA production, rather than transcript-specific sequence features, is the major determinant of nuclear export efficiency of stress-induced transcripts in human cells.
Keywords: mRNA Export , Stress Response , Nuclear Retention