title: Modulation of gene expression by human cytosolic tRNase Z(L) through 5'-half-tRNA.
abstract: A long form (tRNase Z(L)) of tRNA 3' processing endoribonuclease (tRNase Z, or 3' tRNase) can cleave any target RNA at any desired site under the direction of artificial small guide RNA (sgRNA) that mimics a 5'-half portion of tRNA. Based on this enzymatic property, a gene silencing technology has been developed, in which a specific mRNA level can be downregulated by introducing into cells a synthetic 5'-half-tRNA that is designed to form a pre-tRNA-like complex with a part of the mRNA. Recently 5'-half-tRNA fragments have been reported to exist stably in various types of cells, although little is know about their physiological roles. We were curious to know if endogenous 5'-half-tRNA works as sgRNA for tRNase Z(L) in the cells. Here we show that human cytosolic tRNase Z(L) modulates gene expression through 5'-half-tRNA. We found that 5'-half-tRNA(Glu), which co-immunoprecipitates with tRNase Z(L), exists predominantly in the cytoplasm, functions as sgRNA in vitro, and downregulates the level of a luciferase mRNA containing its target sequence in human kidney 293 cells. We also demonstrated that the PPM1F mRNA is one of the genuine targets of tRNase Z(L) guided by 5'-half-tRNA(Glu). Furthermore, the DNA microarray data suggested that tRNase Z(L) is likely to be involved in the p53 signaling pathway and apoptosis.
authors.affiliation: Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
authors.forename: Reyad A
authors.initials: RA
authors.lastname: Elbarbary
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takaku
authors.forename: Naoto
authors.initials: N
authors.lastname: Uchiumi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tamiya
authors.forename: Mayumi
authors.initials: M
authors.lastname: Abe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nashimoto
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D003600:Cytosol / Q000378:metabolism; D004722:Endoribonucleases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence / Q000379:methods; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004722:Endoribonucleases; C531011:tRNase Z, human