Preprint Highlight: A role for phase separation to prevent R-loops during transcription.

Abstract

The RNA-binding protein FUS (FUSed in sarcoma) regulates transcription by binding to polymerases and undergoing phase separation to enrich transcription machinery and RNA processing factors. Using an in vitro transcription assay and a DNA-dependent RNA polymerase from T7 phage (T7 Pol) that does not bind to FUS, this study uncovered a polymerase-binding independent role of FUS in increasing transcription productivity. The ability of FUS to phase separate with RNA prevented RNA-DNA hybrid (R-loop) formation during transcription in vitro and in cells. This work suggests a potential link between the toxicity of FUS mutants in amyotrophic lateral sclerosis or Ewing sarcoma to elevated R-loops and the resulting disruption in gene expression and genome stability.