Gene silencing by the tRNA maturase tRNase ZL under the direction of small-guide RNA
| Autor: | Hirotaka S. Shibata, Hiroaki Takaku, Y Negishi, Masamichi Takagi, Masayuki Nashimoto, Aiko Nakashima, Masato Tamura |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
tRNase ZL
Endoribonuclease Blotting Western Down-Regulation Gene Expression Biology Transfection Glycogen Synthase Kinase 3 Mice RNA Transfer RNA interference Gene expression Endoribonucleases Genetics Gene silencing Animals Humans tRNase Z Guide RNA Gene Silencing RNA Messenger Luciferases Molecular Biology Gene Mice Inbred ICR Glycogen Synthase Kinase 3 beta Reverse Transcriptase Polymerase Chain Reaction RNA Glyceraldehyde-3-Phosphate Dehydrogenases Genetic Therapy Blotting Northern Molecular biology Genes bcl-2 RNAi Transfer RNA Molecular Medicine Female sgRNA Genetic Engineering Plasmids RNA Guide Kinetoplastida |
| Zdroj: | Gene therapy. 14(1) |
| ISSN: | 0969-7128 |
| Popis: | We have been developing a unique system for the downregulation of a gene expression through cutting a specific mRNA by the long form of tRNA 3'-processing endoribonuclease (tRNase Z(L)) under the direction of small-guide RNA (sgRNA). However, the efficacy of this system and the involvement of tRNase Z(L) in the living cells were not clear. Here we show, by targeting the exogenous luciferase gene, that the efficacy of the sgRNA/tRNase Z(L) method can become comparable to that of the RNA interference technology and that the gene silencing is owing to tRNase Z(L) directed by sgRNA not owing to a simple antisense effect. We also show that tRNase Z(L) together with sgRNA can downregulate expression of the endogenous human genes Bcl-2 and glycogen synthase kinase-3beta by degrading their mRNAs in cell culture. Furthermore, we demonstrate that a gene expression in the livers of postnatal mice can be inhibited by an only seven-nucleotide sgRNA. These data suggest that sgRNA might be utilized as therapeutic agents to treat diseases such as cancers and AIDS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|