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The focus of my PhD project is to transcriptionally characterize SCAF1 protein.

Transcription of protein coding genes is a dynamic process dependent on the phosphorylation status of the RNA polymerase II (RNAPII) C-terminal domain (CTD). CTD orchestrates the recruitment of proteins involved in regulation of transcription and co-transcriptional processing. These RNAPII associated factors are crucial for correct mRNA biogenesis and proper gene expression; however, we still have an incomplete understanding of how such proteins regulate co-transcriptional processing.

One family of RNAPII associated factors is the Serine/Arginine (SR)-related CTD associated factors (SCAFs). Although all SCAF proteins contain RNAPII CTD-binding domains and interact with RNAPII, most of them remain uncharacterized. Recently, SCAF4 and SCAF8 were shown to share an essential role as mRNA anti-terminators, by preventing the early mRNA transcript cleavage.

In this project, I aim to describe the role of SCAF1 in transcription and co-transcriptional processing. Interestingly, SCAF1 binds the same RNAPII complexes as SCAF4 and SCAF8. With high-throughput experiments and sophisticated transcriptomic techniques, we show that SCAF1 binds the hyper-phosphorylated CTD of RNAPII and associates with elongation and 3’ end processing factors. Moreover, loss of SCAF1 displays isoform switching, leading to expression of shorter mRNAs originating from early mRNA transcript cleavage events. Together, these results highlight a role of SCAF1 in regulating the nature of the mRNA transcripts in human cells.