Talk abstracts
Talk on Saturday 09:00-09:15am submitted by Bailey Webster
Synthetic assembly of transcriptional condensates by RNA-binding proteins
Bailey Webster (Department of Biological Sciences, Carnegie Mellon University), Grant Mowry, Emily Wang, Steven Smeal, Deyuan Xu, Biplab KC, Huaiying Zhang (Department of Biological Sciences, Carnegie Mellon University), Changfeng Deng, David Chenoweth (Department of Chemistry, University of Pennsylvania), Jonathan Hennigner (Department of Biological Sciences, Carnegie Mellon University)
Abstract:
RNA-binding proteins (RBPs) regulate multiple stages of post-transcriptional gene expression, including functions to modify, splice, export, and translate RNA molecules. Recent evidence has revealed that RBPs may also play direct roles in regulating transcription, but mechanisms accounting for such regulation remain unclear. Select RBPs harbor intrinsically disordered regions (IDRs) with amino acid enrichments similar to transcription factors, suggesting that RBPs could form multivalent interactions with the transcriptional apparatus or even participate in the emergent assembly of transcriptional condensates. Here, we found that select RBP IDRs can directly recruit transcription cofactors using a chemical dimerizer system that generates synthetic and inducible condensates that form on oligomeric seeds. We created stable murine embryonic stem cell lines expressing select protein scaffolds, including several transcription factors, transcriptional cofactors, chromatin modifiers, and RBPs, at sub-saturating concentrations. Condensate formation upon dimerization varied by scaffold, and when condensates did form, they exhibited scaffold-specific nuclear patterning characteristics, including differences in size, number, spacing, and partitioning. Condensates composed of transcription factors were able to partition endogenous transcriptional proteins, a feature one would expect of bona fide transcriptional condensates. Select RBP IDR scaffolds, including HNRNPA1-IDR, were able to recruit endogenous Med1, a component of the Mediator coactivator complex, upon condensate induction in a fashion similar to canonical transcription factors. Together, our results show that select RBPs are capable of recruiting transcriptional cofactors in cells, providing a mechanism for RBP-mediated transcriptional regulation.
Keywords: RNA-binding protein, Biomolecular condensate, Transcription