PT  - JOURNAL ARTICLE
AU  - A. L. Richards
AU  - D. Watza
AU  - A. Findley
AU  - A. Alazizi
AU  - X. Wen
AU  - A. A. Pai
AU  - R. Pique-Regi
AU  - F. Luca
TI  - Environmental perturbations lead to extensive directional shifts in RNA processing
AID  - 10.1101/119974
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 119974
4099  - http://biorxiv.org/content/early/2017/03/24/119974.short
4100  - http://biorxiv.org/content/early/2017/03/24/119974.full
AB  - Environmental perturbations have large effects on both organismal and cellular traits, including gene expression, but the extent to which the environment affects RNA processing remains largely uncharacterized. We assessed changes in RNA processing events across 89 environments in five human cell types and identified 15,628 event shifts (FDR = 15%) comprised of eight event types in 4,567 genes. Many of these changes occur consistently in the same direction across conditions, indicative of global regulation by trans factors. Accordingly, we demonstrate that environmental modulation of binding for splicing factors predicts shifts in intron retention, while binding for transcription factors predicts shifts in AFE usage in response to specific treatments. Further, we validate these findings profiling chromatin accessibility with ATAC-seq in LCLs exposed to selenium. Together, these results demonstrate that RNA processing is dramatically changed in response to specific environmental perturbations through different mechanisms regulated by trans factors.