Alex Francette to Speak

Title: Insights into the Structure, Function and Evolution of a Critical Transcription Elongation Factor

Abstract:

Interactions between RNA Polymerase II (RNAPII) and multitudinous transcription elongation factors facilitate critical co-transcriptional events that regulate the state of chromatin as well as the production and processing of nascent transcripts. The Paf1 Complex (Paf1C) is one such transcription elongation factor that associates with RNAPII during elongation. Disruptions of Paf1C have been linked to various pathologies including Wilms tumor, pancreatic cancer, and malignancies of the parathyroid. While Paf1C is found to contribute to various facets of transcription regulation, disentangling the mechanisms of Paf1C-mediated modulation of co-transcriptional processes remains a challenge. Through a phylogenetic analysis of Paf1C subunits, I have gained insights into the evolution of Paf1C throughout Eukaryota which I can leverage to screen for separation of function mutations in the Paf1C. I have additionally identified what appears to be multiple events of the loss of Paf1C in the Euglenozoa, Metamonad, and SAR clades, suggesting that some evolutionary pressures may render Paf1C dispensable and providing insights into transcriptional regulation in human pathogens such as Toxoplasma gondii, Trypanosoma cruzi, and Giardia intestinalis. Furthermore, I have analyzed the roles of the conserved Trestle and C-terminal domains of the Ctr9 subunit of Paf1C in budding yeast. Utilizing nascent transcriptomics, I have observed that deletion of Trestle and C-terminus of Ctr9 induces apparent misregulation of gene expression, transcript splicing, and RNAPII processivity similar to the loss of Ctr9 entirely. Together, this work sheds light on the history and structural features of a critical, medically relevant transcription elongation factor. 

Arndt Lab

Friday, March 29th, 2024

12:00PM

Langley A219B