Talk abstracts
Talk on Saturday 08:30-08:45am submitted by Haoran Wang
RNA-binding proteins activate transcription through defined molecular grammars
Haoran Wang (Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA), Lydia Phillips, Dervla Moore-Frederick, Bailey K. Webster, Deyuan Xu (Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA), Grant Mowry, Emily Wang, Arth Banka (Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA), Sid Srivastava, Biplab K.C, Huaiying Zhang (Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA), Changfeng Deng, David M. Chenoweth (Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104), Jonathan E. Henninger (Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA)
Abstract:
Transcription and RNA processing have traditionally been considered independent processes, but recent evidence has revealed their biochemical coupling. Transcription factors (TFs) that bind DNA and regulate transcription also interact with RNA and can influence RNA processing. Conversely, RNA-binding proteins (RBPs) that regulate RNA processing localize to gene regulatory elements, and their perturbation causes transcriptional defects. Whether canonical RBPs can directly regulate transcription remains unclear. Here, we find select RBPs activate transcription through latent activation domains akin to TFs. RBP activators regulate distinct genes, a feature not explained by post-transcriptional mechanisms, and interact with transcriptional condensates. RBP activation domains are enriched in aromatic and polar residues but depleted of basic residues features that are conserved, required for activation, and partially mimic TF activation domains. Using this molecular grammar, we predicted and experimentally validated additional RBP IDR activators across the human proteome, including the C-terminal domain (CTD) of RPB1, the largest catalytic subunit of RNA polymerase II. The RPB1 CTD can activate transcription and recruit transcriptional coactivators, revealing a non-enzymatic regulatory function for RNA polymerase II. Together, these findings position RNA processing factors and RPB1 as transcriptional regulators, explain coupling between transcription and co-transcriptional RNA processing, and reveal RNA-RBP regulatory networks that parallel DNA-TF networks.
Keywords: RNA-binding proteins, transcriptional regulation, super-resolution microscopy