The cytoplasmic and nuclear populations of the eukaryote tRNA-isopentenyl transferase have distinct functions with implications in human cancer

Gene. 2015 Feb 1;556(1):13-8. doi: 10.1016/j.gene.2014.09.049. Epub 2014 Sep 26.

Abstract

Mod5 is the yeast tRNA isopentenyl transferase, an enzyme that is conserved from bacteria to humans. Mod5 is primarily cytoplasmic where it modifies the A37 position of a few tRNAs, and the yeast enzyme has been shown capable of forming heritable, amyloid-like aggregates that confer a selective advantage in the presence of specific antifungal agents. A subpopulation of Mod5 is also found associated with nuclear tRNA genes, where it contributes tRNA-gene mediated (tgm) silencing of local transcription by RNA polymerase II. The tgm-silencing function of Mod5 has been observed in yeast and a Mod5-deletion in yeast can be complemented by the plant and human tRNA isopentenyl transferases, but not the bacterial enzymes, possibly due to the lack of an extended C-terminal domain found in eukaryotes. In light of this additional nuclear role for Mod5 we discuss the proposed role of the human homologue of Mod5, TRIT1, as a tumor suppressor protein.

Keywords: Mod5; Prion; TRIT1; Tumor suppressor; tRNA; tRNA gene-mediated silencing; tRNA modification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alkyl and Aryl Transferases / genetics
  • Alkyl and Aryl Transferases / metabolism*
  • Amino Acid Sequence
  • Cell Nucleus / enzymology*
  • Cell Nucleus / metabolism
  • Cytoplasm / enzymology*
  • Cytoplasm / metabolism
  • Genes, Tumor Suppressor
  • Humans
  • Molecular Sequence Data
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Protein Folding
  • Sequence Homology, Amino Acid

Substances

  • Alkyl and Aryl Transferases
  • TRIT1 protein, human