Poster Presentation 16th Asian Conference on Transcription 2019

Structural study on prokaryotic transcription - how RNA polymerases pause and go (1115)

Jin Young Kang 1
  1. KAIST, Daejon, DAEJON, South Korea

The transcriptional pausing plays pivotal roles in transcription initiation, elongation, termination, RNA folding, and translation. In E.coli, RNA polymerase (RNAP) pauses at every ~100 bps during transcription and hairpin structure of nascent RNA increases pause lifetimes ten-fold or more. Despite its central life-maintaining function, the underlying molecular mechanism of transcriptional pausing has remained elusive. To probe this, we determined a 3.8 Å cryo-electron microscopy (cryo-EM) structure of an E. coli his pause elongation complex (hisPEC). From the structure, we found that i) the RNA hairpin stem forms within the RNA exit channel of RNAP, ii) the DNA:RNA hybrid is trapped in a distinctive half-translocated conformation, and iii) mobile domains of the RNAP swiveled in a concerted manner. To understand how these pauses are regulated, we solved structures of anti-pausing factors, NusG- and RfaH-bound elongation complexes at 3.7 Å and 3.5 Å resolution, respectively. These revealed that NusG and RfaH bind to the β protrusion, β gate loop, and β’ clamp helices of RNAP, stabilizing the RNAP in a conformation of active elongation state. While both NusG and RfaH reduce backtrack pausing, only RfaH blocks RNA hairpin-stabilized pausing by binding to the elongation complex tightly enough to resist RNAP swiveling. Based on our results, we propose that the pause RNA hairpin stabilizes global conformational changes in the RNAP that secures the paused state while NusG and RfaH enhance transcription elongation by maintaining the active conformation of the elongation complex.