ArticleRNA biology2015
Toward optimization of AgoshRNA molecules that use a non-canonical RNAi pathway: variations in the top and bottom base pairs.
Article in RNA biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Design of antiviral AGO2-dependent short hairpin RNAs.Virologica Sinica · 2024Article
- One locus, several functional RNAs-emerging roles of the mechanisms responsible for the sequence variability of microRNAs.Biologia futura · 2023Review
- Article
- Gene knockdown in malaria parasites via non-canonical RNAi.Nucleic acids research · 2020Article
- Article
- Influence of a 3' Terminal Ribozyme on AgoshRNA Biogenesis and Activity.Molecular therapy. Nucleic acids · 2019Article
- Influence of the loop size and nucleotide composition on AgoshRNA biogenesis and activity.RNA biology · 2017Article
- Dicer-independent processing of small RNA duplexes: mechanistic insights and applications.Nucleic acids research · 2017Review
- Silencing of HIV-1 by AgoshRNA molecules.Gene therapy · 2017Article
- The influence of the 5΄-terminal nucleotide on AgoshRNA activity and biogenesis: importance of the polymerase III transcription initiation site.Nucleic acids research · 2017Article
- Mutation of nucleotides around the +1 position of type 3 polymerase III promoters: The effect on transcriptional activity and start site usage.Transcription · 2017Article
- Article
- Development of Novel Small Hairpin RNAs That do not Require Processing by Dicer or AGO2.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Off Target, but Sequence-Specific, shRNA-Associated Trans-Activation of Promoter Reporters in Transient Transfection Assays.PloS one · 2016Article
- Bone Marrow Gene Therapy for HIV/AIDS.Viruses · 2015Review
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Short hairpin RNAs (shRNAs) are widely used for gene knockdown by inducing the RNA interference (RNAi) mechanism. The shRNA precursor is processed by Dicer into small interfering RNAs (siRNAs) and subsequently programs the RNAi-induced silencing complex (RISC) to find a complementary target mRNA (mRNA) for post-transcriptional gene silencing. Recent evidence indicates that shRNAs with a relatively short basepaired stem bypass Dicer to be processed directly by the Ago2 nuclease of the RISC complex. We named this design AgoshRNA as these molecules depend on Ago2 both for processing and subsequent silencing activity. This alternative AgoshRNA processing route yields only a single active RNA strand, an important feature to restrict off-target effects induced by the passenger strand of regular shRNAs. It is therefore important to understand this novel AgoshRNA processing route in mechanistic detail such that one can design the most effective and selective RNA reagents. We performed a systematic analysis of the optimal base pair (bp) composition at the top and bottom of AgoshRNA molecules. In this study, we document the importance of the 5' end nucleotide (nt) and a bottom mismatch. The optimized AgoshRNA design exhibits improved RNAi activity across cell types. These results have important implications for the future design of more specific RNAi therapeutics.
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