VapCs of Mycobacterium tuberculosis Cleave RNAs Essential for Translation: VapCs of M. tuberculosis cleave tRNAs and 23S rRNA

David Tollervey, Kristoffer Skovbo Winther, Jai Tree, Kenn Gerdes

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The major human pathogen Mycobacterium tuberculosis 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 sitespecific cleavage of the universally conserved Sarcin-Ricin loop (SRL) in 23S rRNA. Here we identify cleavage targets for 11 VapCs from M. tuberculosis commencing with UV-crosslinking and deep sequencing. Remarkably, these VapCs are all site-specific endoribonucleases that cleave RNA targets that are essential for decoding at the ribosomal A-site. Ten 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
Original languageEnglish
Number of pages12
JournalNucleic Acids Research
Volume44
Issue number15
DOIs
Publication statusPublished - 5 Sept 2016

Keywords / Materials (for Non-textual outputs)

  • VapC
  • translation
  • PIN-domain
  • tRNase
  • rRNase
  • toxin – antitoxin

Fingerprint

Dive into the research topics of 'VapCs of Mycobacterium tuberculosis Cleave RNAs Essential for Translation: VapCs of M. tuberculosis cleave tRNAs and 23S rRNA'. Together they form a unique fingerprint.

Cite this