tRNA modification and cancer: potential for therapeutic prevention and intervention

Future Med Chem. 2019 Apr;11(8):885-900. doi: 10.4155/fmc-2018-0404. Epub 2019 Feb 12.

Abstract

Transfer RNAs (tRNAs) undergo extensive chemical modification within cells through the activity of tRNA methyltransferase enzymes (TRMs). Although tRNA modifications are dynamic, how they impact cell behavior after stress and during tumorigenesis is not well understood. This review discusses how tRNA modifications influence the translation of codon-biased transcripts involved in responses to oxidative stress. We further discuss emerging mechanistic details about how aberrant TRM activity in cancer cells can direct programs of codon-biased translation that drive cancer cell phenotypes. The studies reviewed here predict future preventative therapies aimed at augmenting TRM activity in individuals at risk for cancer due to exposure. They further predict that attenuating TRM-dependent translation in cancer cells may limit disease progression while leaving noncancerous cells unharmed.

Keywords: anticodon; cancer; codon-bias; modification; oxidative stress; tRNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Codon
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Methylation
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Oxidative Stress
  • RNA, Transfer / genetics*
  • RNA, Transfer / metabolism
  • tRNA Methyltransferases / genetics
  • tRNA Methyltransferases / metabolism

Substances

  • Codon
  • RNA, Transfer
  • tRNA Methyltransferases