ArticleCellular and molecular life sciences : CMLS2021
Artificial miRNAs targeting CAG repeat expansion in ORFs cause rapid deadenylation and translation inhibition of mutant transcripts.
Article in Cellular and molecular life sciences : CMLS, 2021. 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, 35 citations in OpenAlex.
- Discovery of a mutation-containing circRNA in polyglutamine disease through systematic analysis of RNAs with CAG repeats.RNA biology · 2026Article
- CAG-targeting artificial miRNA with reduced off-target risk for efficient lowering of pathogenic polyglutamine proteins.NAR molecular medicine · 2026Article
- HTT loss-of-function contributes to RNA deregulation in developing Huntington's disease neurons.Cell & bioscience · 2025Article
- CAG-targeted brain-permeable therapy tested in biallelic humanized polyQ mouse models.Molecular therapy. Nucleic acids · 2025Article
- Insights into RNA-mediated pathology in new mouse models of Huntington's disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- From design to cellular processing: Insights into sequencing of vectorized therapeutic small RNAs.Molecular therapy. Nucleic acids · 2024Article
- Sequencing-guided design of genetically encoded small RNAs targeting CAG repeats for selective inhibition of mutantMolecular therapy. Nucleic acids · 2024Article
- AAV-Mediated CAG-Targeting Selectively Reduces Polyglutamine-Expanded Protein and Attenuates Disease Phenotypes in a Spinocerebellar Ataxia Mouse Model.International journal of molecular sciences · 2024Article
- Development of super-specific epigenome editing by targeted allele-specific DNA methylation.Epigenetics & chromatin · 2023Article
- Allele-specific quantitation of ATXN3 and HTT transcripts in polyQ disease models.BMC biology · 2023Article
- RNA regulation in brain function and disease 2022 (NeuroRNA): A conference report.Frontiers in molecular neuroscience · 2023Review
- A CAG repeat-targeting artificial miRNA lowers the mutant huntingtin level in the YAC128 model of Huntington's disease.Molecular therapy. Nucleic acids · 2022Article
- Review
- Emerging Therapies for Huntington's Disease - Focus on N-Terminal Huntingtin and Huntingtin Exon 1.Biologics : targets & therapy · 2022Review
- The Novel Role of hnRNP UL1 in Human Cell Nucleoli.International journal of biological sciences · 2022Article
- Ataxin-2 gene: a powerful modulator of neurological disorders.Current opinion in neurology · 2021Review
- Regulatory Potential of Competing Endogenous RNAs in Myotonic Dystrophies.International journal of molecular sciences · 2021Review
- What, When and How to Measure-Peripheral Biomarkers in Therapy of Huntington's Disease.International journal of molecular sciences · 2021Review
- Establishing resources and increasing awareness to advance research on Dentatorubral-pallidoluysian atrophy toward a treatment: a patient organization perspective.Therapeutic advances in rare diseaseReview
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Polyglutamine (polyQ) diseases are incurable neurological disorders caused by CAG repeat expansion in the open reading frames (ORFs) of specific genes. This type of mutation in the HTT gene is responsible for Huntington's disease (HD). CAG repeat-targeting artificial miRNAs (art-miRNAs) were shown as attractive therapeutic approach for polyQ disorders as they caused allele-selective decrease in the level of mutant proteins. Here, using polyQ disease models, we aimed to demonstrate how miRNA-based gene expression regulation is dependent on target sequence features. We show that the silencing efficiency and selectivity of art-miRNAs is influenced by the localization of the CAG repeat tract within transcript and the specific sequence context. Furthermore, we aimed to reveal the events leading to downregulation of mutant polyQ proteins and found very rapid activation of translational repression and HTT transcript deadenylation. Slicer-activity of AGO2 was dispensable in this process, as determined in AGO2 knockout cells generated with CRISPR-Cas9 technology. We also showed highly allele-selective downregulation of huntingtin in human HD neural progenitors (NPs). Taken together, art-miRNA activity may serve as a model of the cooperative activity and targeting of ORF regions by endogenous miRNAs.
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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.