Mechanism for the Regulated Control of Transcription Termination by a Universal Adapter Protein

Abstract

NusG/Spt5 proteins are the only transcription factors utilized by all cellular organisms. In enterobacteria, NusG antagonizes the transcription termination activity of Rho, a hexameric helicase and functional analog of eukaryotic Sen1, during transcription of ribosomal and actively translated mRNAs. Paradoxically, NusG helps Rho act on untranslated transcripts, including non-canonical antisense RNAs or those arising from translational stress; how NusG fulfills these disparate functions is unknown. Here, we demonstrate that NusG activates Rho by assisting helicase isomerization from an open-ring, RNA-loading state to a closed-ring, catalytically-active translocase. A crystal structure of closed-ring Rho in complex with NusG reveals the physical basis for this activation, and further explains how Rho is excluded from translationally-competent RNAs. This study demonstrates how a universally conserved transcription factor acts to modulate the activity of a ring-shaped ATPase motor, and establishes how the innate sequence-bias of a termination factor can be modulated to silence pervasive, aberrant transcription.