Poster abstracts
Poster number 71 submitted by Steven Smeal
Disease-causing mutations disrupt the co-patterning of transcriptional and RNA processing condensates
Steven W Smeal (Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213), Deyuan Xu (Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213), Mary Skillicorn (Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208), Lydia Phillips, Haoran Wang, Grant Mowry, Nic Fitzgerald (Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213), Krishna Shrinivas (Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208), Jonathan Henninger (Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213)
Abstract:
Transcription and RNA processing are coupled processes in gene expression that are organized by biomolecular condensates in the nucleus. How these condensates are physically patterned – including their size, number, spacing, partitioning, and colocalization, how they change relative to one another during transcription, and the regulatory mechanisms that govern this patterning all remain unknown. Here, using endogenous fluorescent tagging and lattice structured illumination microscopy in live cells, we find that transcriptional and RNA splicing condensates form interfacial interactions (“cuddling”) at condensate boundaries in a manner similar to transcriptional and RNA processing condensates in the nucleolus. Disruption of either transcription or splicing alters the cuddling interaction. Through experiment and physical simulation, we find that co-patterning of nuclear or nucleolar condensates depends on a non-equilibrium state driven by local RNA synthesis and principles of complex coacervation. Mutations in RNA-binding proteins that cause myeloid disorders and leukemia disrupt proper co-patterning of transcriptional and splicing condensates, suggesting that alteration of emergent organization in transcription and splicing contributes to oncogenesis. Together, our results provide evidence that physicochemical mechanisms driven by RNA synthesis underlie the emergent patterning and coupling of transcription and RNA processing in gene expression.
Keywords: Transcription, Splicing, Biomolecular condensates