ArticleNucleic acids research2003
Short hairpin type of dsRNAs that are controlled by tRNA(Val) promoter significantly induce RNAi-mediated gene silencing in the cytoplasm of human cells.
Article in Nucleic acids research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 260 citations in OpenAlex.
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- Non-viral nucleic acid containing nanoparticles as cancer therapeutics.Expert opinion on drug delivery · 2016Review
- Bioreducible Poly(Beta-Amino Ester)s for Intracellular Delivery of SiRNA.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Design and characterization of a new peptide vector for short interfering RNA delivery.Journal of nanobiotechnology · 2015Article
- Article
- Dicer-independent processing of short hairpin RNAs.Nucleic acids research · 2013Article
- Lentiviral miR30-based RNA interference against heparanase suppresses melanoma metastasis with lower liver and lung toxicity.International journal of biological sciences · 2013Article
- MicroRNAs in Head and Neck Cancer.International journal of dentistry · 2013Review
- Illuminating the gateway of gene silencing: perspective of RNA interference technology in clinical therapeutics.Molecular biotechnology · 2012Review
- MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review.EMBO molecular medicine · 2012Review
- Strand antagonism in RNAi: an explanation of differences in potency between intracellularly expressed siRNA and shRNA.Nucleic acids research · 2012Article
- Personalized cancer approach: using RNA interference technology.World journal of surgery · 2011Review
- Efficient downregulation of multiple mRNA targets with a single shRNA-expressing lentiviral vector.Plasmid · 2010Article
- Novel RNA-based strategies for therapeutic gene silencing.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Review
- Allele-specific RNAi mitigates phenotypic progression in a transgenic model of Alzheimer's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
- Peculiarities of piRNA-mediated post-transcriptional silencing of Stellate repeats in testes of Drosophila melanogaster.Nucleic acids research · 2009Article
- Short non-coding RNA biology and neurodegenerative disorders: novel disease targets and therapeutics.Human molecular genetics · 2009Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The post-transcriptional gene silencing in animals and plants is called RNA interference (RNAi). Guides for the sequence-specific degradation of mRNA are 21-nt small interfering RNAs (siRNAs) that are generated by Dicer-dependent cleavage from longer double-stranded RNAs (dsRNAs). To examine the relationship between the localization of dsRNA and the target cleavage of RNAi in human cells, we constructed five kinds of dsRNA expression vector that were controlled by tRNA(Val) or U6 promoter. Transcripts of tRNA-dsRNA were consistently localized in the cytoplasm and were efficiently processed by Dicer. In contrast, transcripts of tRNA-dsRNA were not processed in cells that expressed Dicer-directed ribozymes. In addition, transcripts of U6-dsRNA were basically localized in the nucleus and were not significantly processed, unless the transcripts of U6-dsRNAs possessed a microRNA-based loop motif: in the latter case, U6-dsRNAs with a microRNA-based loop were transported to the cytoplasm and were effectively processed. More over, tRNA-dsRNA directed against a mutant k-ras transcript cleaved its target mRNA efficiently in assays of RNAi not only in vitro with a cytoplasmic extract but also in vivo. Therefore, it appears that RNAi in human cells occur in the cytoplasm. Importantly, the same tRNA-dsRNA did not affect the degradation of the normal k-ras mRNA in vitro and in vivo. Our tRNA-dsRNA technology should be a powerful tool for studies of the mechanism of RNAi and the functions of various genes in mammalian cells with potential utility as a therapeutic agent.
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