ArticleJournal of virology1999
Factors governing the activity in vivo of ribozymes transcribed by RNA polymerase III.
Article in Journal of virology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 88 citations in OpenAlex.
- Prevention of ribozyme catalysis through cDNA synthesis enables accurate RT-qPCR measurements of context-dependent ribozyme activity.RNA (New York, N.Y.) · 2025Article
- Development and application of ribonucleic acid therapy strategies against COVID-19.International journal of biological sciences · 2022Review
- Gene editing and RNAi approaches for COVID-19 diagnostics and therapeutics.Gene therapy · 2021Review
- Article
- Relieving bottlenecks in RNA drug discovery for retinal diseases.Advances in experimental medicine and biology · 2012Review
- Variables and strategies in development of therapeutic post-transcriptional gene silencing agents.Journal of ophthalmology · 2011Article
- Novel RNA-based strategies for therapeutic gene silencing.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Review
- Effective suppression of Dengue fever virus in mosquito cell cultures using retroviral transduction of hammerhead ribozymes targeting the viral genome.Virology journal · 2009Article
- Development of lead hammerhead ribozyme candidates against human rod opsin mRNA for retinal degeneration therapy.Experimental eye research · 2009Article
- A triplex ribozyme expression system based on a single hairpin ribozyme.Oligonucleotides · 2008Article
- Targeting Alzheimer's disease genes with RNA interference: an efficient strategy for silencing mutant alleles.Nucleic acids research · 2004Article
- Truncated product of the bifunctional DLST gene involved in biogenesis of the respiratory chain.The EMBO journal · 2003Article
- Targeting mortalin using conventional and RNA-helicase-coupled hammerhead ribozymes.EMBO reports · 2003Article
- Identification of genes involved in cell invasion by using a library of randomized hybrid ribozymes.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- Short hairpin type of dsRNAs that are controlled by tRNA(Val) promoter significantly induce RNAi-mediated gene silencing in the cytoplasm of human cells.Nucleic acids research · 2003Article
- Significantly higher activity of a cytoplasmic hammerhead ribozyme than a corresponding nuclear counterpart: engineered tRNAs with an extended 3' end can be exported efficiently and specifically to the cytoplasm in mammalian cells.Nucleic acids research · 2001Article
- RNA-protein hybrid ribozymes that efficiently cleave any mRNA independently of the structure of the target RNA.Proceedings of the National Academy of Sciences of the United States of America · 2001Article
- Reduction of target gene expression by a modified U1 snRNA.Molecular and cellular biology · 2001Article
- tRNAVal-heterodimeric maxizymes with high potential as geneinactivating agents: simultaneous cleavage at two sites in HIV-1 Tat mRNA in cultured cells.Proceedings of the National Academy of Sciences of the United States of America · 1999Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In order to determine the parameters that govern the activity of a ribozyme in vivo, we made a systematic analysis of chimeric tRNAVal ribozymes by measuring their cleavage activities in vitro as well as the steady-state levels of transcripts, the half-lives of transcribed tRNAVal ribozymes, and their activities in both HeLa and H9 cells. These analyses were conducted by the use of transient expression systems in HeLa cells and stable transformants that express ribozymes. Localization of transcripts appeared to be determined by the higher-order structure of each transcribed tRNAVal ribozyme. Since colocalization of the ribozyme with its target RNA is important for strong activity of the ribozyme in vivo, the best system for tRNA-based expression seems to be one in which the structure of the transcript is different from that of the natural tRNA precursor so that processing of the tRNAVal ribozyme can be avoided. At the same time, the structure of the transcript must be similar enough to allow recognition, probably by an export receptor, so that the transcript can be exported to the cytoplasm to ensure colocalization with its target. In the case of several tRNAVal ribozymes that we constructed, inspection of computer-predicted secondary structures enabled us to control the export of transcripts. We found that only a ribozyme that was transcribed at a high level and that had a sufficiently long half-life, within cells, had significant activity when used to withstand a challenge by human immunodeficiency virus type 1.
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