Nascent RNA-mediated recruitment and R-loop suppression underlie FUS-driven enhancement of transcription

Biomolecular condensates have been proposed to enhance transcription by locally concentrating polymerases and cofactors, often through intrinsically disordered proteins. However, the functional role of phase separation and the molecular connections between RNA and the transcription machinery remain poorly defined. Using T7 RNA polymerase (T7 RNAP), which lacks intrinsic disorder, together with FUS, which does not directly interact with T7 RNAP, we dissect the mechanisms by which FUS enhances transcription. We find that monomeric FUS is sufficient to stimulate transcription, whereas condensate formation contributes only a modest additional effect. FUS is recruited selectively to active transcription complexes through binding to nascent RNA, assembling into a dynamic nanoscale structure that enhances RNAP loading and stabilizes the transcription initiation bubble. Furthermore, FUS suppresses inhibitory R-loop formation, thereby accelerating elongation. Together, these findings identify nascent RNA as the central organizing element through which FUS modulates transcription via specific molecular interactions, largely independent of phase separation. RNA-binding proteins are thought to enhance transcription by forming condensates. Here, the authors show that nascent RNA recruits FUS to boost polymerase loading and accelerate elongation by preventing R-loops, without requiring macroscopic condensates.