Modulation of gene expression by human cytosolic tRNase ZL through 5′-half-tRNA

Reyad Elbarbary, Hiroaki Takaku, Naoto Uchiumi, Hiroko Tamiya, Mayumi Abe, Masayuki Takahashi, Hiroshi Nishida, Masayuki Nashimoto

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

A long form (tRNase ZL) 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 ZL in the cells. Here we show that human cytosolic tRNase ZL modulates gene expression through 5′-half-tRNA. We found that 5′-half-tRNA Glu, 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 5′-half-tRNA Glu, Furthermore, the DNA microarray data suggested that tRNase ZL is likely to be involved in the p53 signaling pathway and apoptosis.

Original languageEnglish (US)
Article numbere5908
JournalPLoS One
Volume4
Issue number6
DOIs
StatePublished - Jun 15 2009

Fingerprint

Transfer RNA
Gene expression
Guide RNA
Modulation
RNA
Gene Expression
RNA, Transfer, Glu
gene expression
Messenger RNA
endoribonucleases
Down-Regulation
Artificial Cells
gene silencing
luciferase
kidney cells
RNA Precursors
Gene Silencing
Microarrays
Oligonucleotide Array Sequence Analysis
Luciferases

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Elbarbary, R., Takaku, H., Uchiumi, N., Tamiya, H., Abe, M., Takahashi, M., ... Nashimoto, M. (2009). Modulation of gene expression by human cytosolic tRNase ZL through 5′-half-tRNA. PLoS One, 4(6), [e5908]. https://doi.org/10.1371/journal.pone.0005908
Elbarbary, Reyad ; Takaku, Hiroaki ; Uchiumi, Naoto ; Tamiya, Hiroko ; Abe, Mayumi ; Takahashi, Masayuki ; Nishida, Hiroshi ; Nashimoto, Masayuki. / Modulation of gene expression by human cytosolic tRNase ZL through 5′-half-tRNA. In: PLoS One. 2009 ; Vol. 4, No. 6.
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abstract = "A long form (tRNase ZL) 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 ZL in the cells. Here we show that human cytosolic tRNase ZL modulates gene expression through 5′-half-tRNA. We found that 5′-half-tRNA Glu, 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 5′-half-tRNA Glu, Furthermore, the DNA microarray data suggested that tRNase ZL is likely to be involved in the p53 signaling pathway and apoptosis.",
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Elbarbary, R, Takaku, H, Uchiumi, N, Tamiya, H, Abe, M, Takahashi, M, Nishida, H & Nashimoto, M 2009, 'Modulation of gene expression by human cytosolic tRNase ZL through 5′-half-tRNA', PLoS One, vol. 4, no. 6, e5908. https://doi.org/10.1371/journal.pone.0005908

Modulation of gene expression by human cytosolic tRNase ZL through 5′-half-tRNA. / Elbarbary, Reyad; Takaku, Hiroaki; Uchiumi, Naoto; Tamiya, Hiroko; Abe, Mayumi; Takahashi, Masayuki; Nishida, Hiroshi; Nashimoto, Masayuki.

In: PLoS One, Vol. 4, No. 6, e5908, 15.06.2009.

Research output: Contribution to journalArticle

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T1 - Modulation of gene expression by human cytosolic tRNase ZL through 5′-half-tRNA

AU - Elbarbary, Reyad

AU - Takaku, Hiroaki

AU - Uchiumi, Naoto

AU - Tamiya, Hiroko

AU - Abe, Mayumi

AU - Takahashi, Masayuki

AU - Nishida, Hiroshi

AU - Nashimoto, Masayuki

PY - 2009/6/15

Y1 - 2009/6/15

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