Open AccessModulation of Gene Expression by Human Cytosolic tRNase ZL through 5′-Half-tRNA
Author(s) -
Reyad A. Elbarbary,
Hiroaki Takaku,
Naoto Uchiumi,
Hiroko Tamiya,
Mayumi Abé,
Masayuki Takahashi,
Hiroshi Nishida,
Masayuki Nashimoto
Publication year - 2009
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0005908
Subject(s) - transfer rna , biology , endoribonuclease , rnase p , rna , gene , gene expression , messenger rna , microbiology and biotechnology , gene silencing , genetics
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.