%0 Journal Article
%T Modulation of Gene Expression by Human Cytosolic tRNase ZL through 5กไ-Half-tRNA
%A Reyad A. Elbarbary
%A Hiroaki Takaku
%A Naoto Uchiumi
%A Hiroko Tamiya
%A Mayumi Abe
%A Masayuki Takahashi
%A Hiroshi Nishida
%A Masayuki Nashimoto
%J PLOS ONE
%D 2009
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0005908
%X A long form (tRNase ZL) of tRNA 3กไ processing endoribonuclease (tRNase Z, or 3กไ tRNase) can cleave any target RNA at any desired site under the direction of artificial small guide RNA (sgRNA) that mimics a 5กไ-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 5กไ-half-tRNA that is designed to form a pre-tRNA-like complex with a part of the mRNA. Recently 5กไ-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 5กไ-half-tRNA works as sgRNA for tRNase ZL in the cells. Here we show that human cytosolic tRNase ZL modulates gene expression through 5กไ-half-tRNA. We found that 5กไ-half-tRNAGlu, which co-immunoprecipitates with tRNase ZL, 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 ZL guided by 5กไ-half-tRNAGlu. Furthermore, the DNA microarray data suggested that tRNase ZL is likely to be involved in the p53 signaling pathway and apoptosis.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005908