Heat Shock Induces Premature Transcript Termination and Reconfigures the Human Transcriptome

The heat shock (HS) response involves rapid induction of HS genes, while transcriptional repression is established more slowly at most other genes. Previous data indicated that such repression might result from inhibition of RNA polymerase II (RNAPII) pause-release, but here we show that HS strongly affects other phases of the transcription cycle. Intriguingly, while elongation rates increase upon HS, processivity markedly decreases so that RNAPII frequently fails to reach the end of genes. Indeed, HS results in widespread premature transcript termination at cryptic poly-adenylation sites near gene 5’-ends via inhibition of U1 telescripting. This results in dramatic reconfiguration of the human transcriptome with production of new, previously unannotated, short mRNAs. Together, these results shed new light on the basic transcription mechanisms induced by growth at elevated temperature and provide the first example of a physiological role for suppression of telescripting.