RNA polymerase II elongation rate controls gene expression by alternative polyadenylation

To study the impact of the RNA polymerase II (Pol II) elongation rate on gene expression, we used CRISPR-Cas9 genome editing in S. pombe to generate a "slow" Pol II mutant with decreased elongation rate. Although the mutation is well tolerated as far as cell growth is concerned, transcriptomic analyses revealed that the slow mutant tends to terminate transcription prematurely. We distinguished two mechanisms by which premature termination affects gene expression in the slow mutant: It either (1) shortens 3'UTR, or (2) derepresses protein coding genes by prematurely terminating upstream interfering RNAs. Strikingly, the genes affected by these mechanisms are enriched for genes involved in phosphate uptake and purine synthesis, two processes essential for the maintenance of the nucleotide pool of the cell. Together with evidences that nucleotides are conditional for Pol II processive elongation, our results suggest that Pol II elongation rate acts as both sensor and effector in response to nucleotide depletion. RNA-seq of Rpb1 N494D S. pombe mutant (2 independent clones) vs wild-type (parental strain)