Bachand, Francois (Université de Sherbrooke)

Purpose

3’ end processing is a fundamental step of gene expression that precedes RNA polyadenylation and that is intimately associated with transcription termination. 3’ end processing is a co-transcriptional process that involves the recruitment of RNA maturation factors by the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAPII). Despite a somewhat fair assessment of the players implicated in RNA processing, much is still unknown about the regulatory mechanisms underlying their integration with the transcription cycle. This is particularly true for 3’ end processing and transcription termination. Indeed, recent transcriptome-wide studies indicate that multiple polyadenylation sites (PAS) are used at most eukaryotic genes, as demonstrated in humans, mouse, plants, flies, and yeast. This process, known as alternative polyadenylation (APA), is emerging as a major layer of gene regulation, allowing the inclusion or exclusion of sequences that control the localization, stability, and translation of mRNAs. However, the mechanism of PAS recognition and how PAS selection is coordinated with transcription termination remains unclear. The long-term goal of our research program is therefore to elucidate the molecular basis by which co-transcriptional 3’ end processing and transcription termination determine the fate of cellular RNAs.