tRNAs Taking Charge

Pathog Dis. 2016 Mar;74(2):ftv117. doi: 10.1093/femspd/ftv117. Epub 2015 Dec 10.

Abstract

Most bacterial toxins derived from chromosomally encoded toxin-antitoxin (TA) systems that have been studied to date appear to protect cells from relatively short pulses of stress by triggering a reversible state of growth arrest. In contrast to many bacterial toxins that are produced as defense mechanisms and secreted from their hosts, TA toxins exert their protective effect from within the cell that produces them. TA toxin-mediated growth arrest is most frequently achieved through their ability to selectively cleave RNA species that participate in protein synthesis. Until very recently, it was thought that the primary conduit for toxin-mediated translation inhibition was cleavage of a single class of RNA, mRNA, thus depleting transcripts and precluding production of essential proteins. This minireview focuses on how the development and implementation of a specialized RNA-seq method to study Mycobacterium tuberculosis TA systems enabled the identification of unexpected RNA targets for toxins, i.e. a handful of tRNAs that are cleaved into tRNA halves. Our result brings to light a new perspective on how these toxins may act in this pathogen and uncovers a striking parallel to signature features of the eukaryotic stress response.

Keywords: Rny1; VapC; angiogenin; antitoxin; toxin; translation inhibition.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antitoxins / chemistry
  • Antitoxins / genetics*
  • Antitoxins / metabolism
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / genetics*
  • Bacterial Toxins / metabolism
  • Colicins / genetics
  • Gene Expression Regulation, Bacterial
  • Humans
  • Inverted Repeat Sequences
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / metabolism
  • Nucleic Acid Conformation
  • RNA, Bacterial / chemistry
  • RNA, Bacterial / genetics*
  • RNA, Bacterial / metabolism
  • RNA, Transfer / chemistry
  • RNA, Transfer / genetics*
  • RNA, Transfer / metabolism
  • Ribonuclease, Pancreatic / genetics
  • Ribonuclease, Pancreatic / metabolism
  • Sequence Analysis, RNA
  • Stress, Physiological
  • Tuberculosis / virology*

Substances

  • Antitoxins
  • Bacterial Toxins
  • Colicins
  • RNA, Bacterial
  • RNA, Transfer
  • angiogenin
  • Ribonuclease, Pancreatic