8e8m
Mycobacterium tuberculosis RNAP paused elongation complex
Structural highlights
FunctionRPOA_MYCTU DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_00059][1] Publication Abstract from PubMedTranscriptional pauses mediate regulation of RNA biogenesis. DNA-encoded pause signals trigger pausing by stabilizing RNA polymerase (RNAP) swiveling and inhibiting DNA translocation. The N-terminal domain (NGN) of the only universal transcription factor, NusG/Spt5, modulates pausing through contacts to RNAP and DNA. Pro-pausing NusGs enhance pauses, whereas anti-pausing NusGs suppress pauses. Little is known about pausing and NusG in the human pathogen Mycobacterium tuberculosis (Mtb). We report that MtbNusG is pro-pausing. MtbNusG captures paused, swiveled RNAP by contacts to the RNAP protrusion and nontemplate-DNA wedged between the NGN and RNAP gate loop. In contrast, anti-pausing Escherichia coli (Eco) NGN contacts the MtbRNAP gate loop, inhibiting swiveling and pausing. Using CRISPR-mediated genetics, we show that pro-pausing NGN is required for mycobacterial fitness. Our results define an essential function of mycobacterial NusG and the structural basis of pro- versus anti-pausing NusG activity, with broad implications for the function of all NusG orthologs. Structural and functional basis of the universal transcription factor NusG pro-pausing activity in Mycobacterium tuberculosis.,Delbeau M, Omollo EO, Froom R, Koh S, Mooney RA, Lilic M, Brewer JJ, Rock J, Darst SA, Campbell EA, Landick R Mol Cell. 2023 May 4;83(9):1474-1488.e8. doi: 10.1016/j.molcel.2023.04.007. Epub , 2023 Apr 27. PMID:37116494[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
