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VapCs of Mycobacterium tuberculosis cleave RNAs essential for translation

Kristoffer Winther1,2, Jai J Tree3, David Tollervey4

  • 1Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark kristoffer.winther@bio.ku.dk.

Nucleic Acids Research
|September 8, 2016
PubMed

Insights

Twelve VapC toxins from Mycobacterium tuberculosis cleave essential RNAs, including tRNAs and the Sarcin-Ricin loop, to reduce translation. This mechanism helps the bacteria persist in hosts for decades.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Mycobacterium tuberculosis persists in hosts for decades by utilizing Toxin-Antitoxin (TA) modules.
  • The vapBC gene family, comprising 48 TA modules, is crucial for this persistence.
  • VapC toxins are PIN domain endonucleases that regulate translation.

Purpose of the Study:

  • To identify the cellular targets of 12 VapC toxins from M. tuberculosis.
  • To understand the role of VapC toxins in bacterial persistence.

Main Methods:

  • UV-crosslinking coupled with deep sequencing was employed to identify RNA targets.
  • Analysis of toxin activity on specific RNA substrates.

Main Results:

  • All 12 studied VapC toxins function as endoribonucleases.
  • Eleven VapC toxins cleave specific tRNAs essential for translation.
  • One VapC toxin (VapC20) cleaves the Sarcin-Ricin loop (SRL) in 23S rRNA.

Conclusions:

  • Multiple VapC toxins contribute to M. tuberculosis survival by inhibiting translation.
  • Targeting essential RNAs, including tRNAs and rRNA, is a key strategy for bacterial persistence.
  • These findings elucidate a novel mechanism of translational control in bacterial survival.

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