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VapCs of Mycobacterium tuberculosis cleave RNAs essential for translation

Lookup NU author(s): Dr Kristoffer Winther, Professor Kenn Gerdes

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).

Abstract

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.

Publication metadata

Author(s): Winther K, Tree JJ, Tollervey D, Gerdes K

Publication type: Article

Publication status: Published

Journal: Nucleic Acids Research

Year: 2016

Volume: 44

Issue: 20

Pages: 9860-9871

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

URL: http://dx.doi.org/10.1093/nar/gkw781

DOI: 10.1093/nar/gkw781

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