Lookup NU author(s): Dr Kristoffer Winther,
Professor Kenn Gerdes
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
The major human pathogen Mycobacterium tubercu-losis can survive in the host organism for decades without causing symptoms. A large cohort of Toxin-Antitoxin (TA) modules contribute to this persistence. Of these, 48 TA modules belong to the vapBC (virulence associated protein) gene family. VapC toxins are PIN domain endonucleases that, in enterobacteria, inhibit translation by site-specific cleavage of initiator tRNA. In contrast, VapC20 of M. tuberculosis inhibits translation by site-specific cleavage of the universally conserved Sarcin-Ricin loop (SRL) in 23S rRNA. Here we identify the cellular targets of 12 VapCs from M. tuberculosis by applying UV-crosslinking and deep sequencing. Remarkably, these VapCs are all endoribonucleases that cleave RNAs essential for decoding at the ribosomal A-site. Eleven VapCs cleave specific tRNAs while one exhibits SRL cleavage activity. These findings suggest that multiple vapBC modules contribute to the survival of M. tuberculosis in its human host by reducing the level of translation.
Author(s): Winther K, Tree JJ, Tollervey D, Gerdes K
Publication type: Article
Publication status: Published
Journal: Nucleic Acids Research
Print publication date: 01/11/2016
Online publication date: 06/09/2016
Acceptance date: 25/08/2016
Date deposited: 27/03/2017
ISSN (print): 0305-1048
ISSN (electronic): 1362-4962
Publisher: Oxford University Press
Altmetrics provided by Altmetric