Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Modulation of gene expression by human cytosolic tRNase Z(L) through 5'-half-tRNA. 1952 60

RNase Z(L) is a highly conserved tRNA 3'-end processing endoribonuclease. Similar to its mammalian counterpart, Drosophila RNase Z(L) (dRNaseZ) has a mitochondria targeting signal (MTS) flanked by two methionines at the N-terminus. Alternative translation initiation yields two protein forms: the long one is mitochondrial, and the short one may localize in the nucleus or cytosol. Here, we have generated a mitochondria specific knockout of the dRNaseZ gene. In this in vivo model, cells deprived of dRNaseZ activity display impaired mitochondrial polycistronic transcript processing, increased reactive oxygen species (ROS) and a switch to aerobic glycolysis compensating for cellular ATP. Damaged mitochondria impose a cell cycle delay at the G2 phase disrupting cell proliferation without affecting cell viability. Antioxidants attenuate genotoxic stress and rescue cell proliferation, implying a critical role for ROS. We suggest that under a low-stress condition, ROS activate tumor suppressor p53, which modulates cell cycle progression and promotes cell survival. Transcriptional profiling of p53 targets confirms upregulation of antioxidant and cycB-Cdk1 inhibitor genes without induction of apoptotic genes. This study implicates Drosophila RNase Z(L) in a novel retrograde signaling pathway initiated by the damage in mitochondria and manifested in a cell cycle delay before the mitotic entry.
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PMID:Knockout of Drosophila RNase ZL impairs mitochondrial transcript processing, respiration and cell cycle progression. 2655 8