ArticleRNA biology2015
Mechanistic insights on the Dicer-independent AGO2-mediated processing of AgoshRNAs.
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 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed.
- Review
- Design of antiviral AGO2-dependent short hairpin RNAs.Virologica Sinica · 2024Article
- Structural Modifications of siRNA Improve Its Performance In Vivo.International journal of molecular sciences · 2023Review
- Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice.Nature communications · 2022Article
- Article
- Endogenous MicroRNA Competition as a Mechanism of shRNA-Induced Cardiotoxicity.Molecular therapy. Nucleic acids · 2020Article
- The Role of MicroRNAs in Diabetes-Related Oxidative Stress.International journal of molecular sciences · 2019Review
- The relevance of microRNA in post-infarction left ventricular remodelling and heart failure.Heart failure reviews · 2019Review
- Micromanaging aerobic respiration and glycolysis in cancer cells.Molecular metabolism · 2019Review
- Hepatic Ago2-mediated RNA silencing controls energy metabolism linked to AMPK activation and obesity-associated pathophysiology.Nature communications · 2018Article
- A New Insight into the Roles of MiRNAs in Metabolic Syndrome.BioMed research international · 2018Review
- Dicer-independent processing of small RNA duplexes: mechanistic insights and applications.Nucleic acids research · 2017Review
- SmithRNAs: Could Mitochondria "Bend" Nuclear Regulation?Molecular biology and evolution · 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
- Blocking sense-strand activity improves potency, safety and specificity of anti-hepatitis B virus short hairpin RNA.EMBO molecular medicine · 2016Article
- Recent advances in RNAi-based strategies for therapy and prevention of HIV-1/AIDS.Advanced drug delivery reviews · 2016Review
- 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
- Guidelines for the optimal design of miRNA-based shRNAs.Methods (San Diego, Calif.) · 2016Review
- MicroRNAs Are Involved in the Development of Morphine-Induced Analgesic Tolerance and Regulate Functionally Relevant Changes in Serpini1.Frontiers in molecular neuroscience · 2016Article
- Bone Marrow Gene Therapy for HIV/AIDS.Viruses · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 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, both for research and therapeutic purposes. The shRNA precursor is processed by the RNase III-like enzyme Dicer into biologically active small interfering RNA (siRNA). This effector molecule subsequently targets a complementary mRNA for destruction via the Argonaute 2 (AGO2) complex. The cellular role of Dicer concerns the processing of pre-miRNAs into mature microRNA (miRNA). Recently, a non-canonical pathway was reported for the biogenesis of miR-451, which bypasses Dicer and is processed instead by the slicer activity of AGO2, followed by the regular AGO2-mediated mRNA targeting step. Interestingly, shRNA designs that are characterized by a relatively short basepaired stem also bypass Dicer to be processed by AGO2. We named this design AgoshRNA as these molecules depend on AGO2 both for processing and silencing activity. In this study, we investigated diverse mechanistic aspects of this new class of AgoshRNA molecules. We probed the requirements for AGO2-mediated processing of AgoshRNAs by modification of the proposed cleavage site in the hairpin. We demonstrate by deep sequencing that AGO2-processed AgoshRNAs produce RNA effector molecules with more discrete ends than the products of the regular shRNA design. Furthermore, we tested whether trimming and tailing occurs upon AGO2-mediated processing of AgoshRNAs, similar to what has been described for miR-451. Finally, we tested the prediction that AgoshRNA activity, unlike that of regular shRNAs, is maintained in Dicer-deficient cell types. These mechanistic insights could aid in the design of optimised AgoshRNA tools and therapeutics.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.