title: The cytoplasmic and nuclear populations of the eukaryote tRNA-isopentenyl transferase have distinct functions with implications in human cancer.
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.
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: smaldino@med.umich.edu.
authors.forename: P J
authors.initials: PJ
authors.lastname: Smaldino
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Read
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA; The Great Plains Laboratory, 11813W. 77th St. Lenexa KS 66214, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pratt-Hyatt
authors.affiliation: Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Hopper
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: engelke@med.umich.edu.
authors.forename: D R
authors.initials: DR
authors.lastname: Engelke
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000201:enzymology* / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology* / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid
chemical_list: D019883:Alkyl and Aryl Transferases; C000595656:TRIT1 protein, human
keywords: Mod5; Prion; TRIT1; Tumor suppressor; tRNA; tRNA gene-mediated silencing; tRNA modification