ArticleBiochemistry2013
Role of context in RNA structure: flanking sequences reconfigure CAG motif folding in huntingtin exon 1 transcripts.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Human-specific sequence features in HTT exon 1 promote toxic misprocessing via splicing factor SRSF7.Nature communications · 2026Article
- Pathogenic CGG expansions in oculopharyngodistal myopathy exhibit distinct characteristics of each causative gene on the flanking sequences as well as methylation status.Genome medicine · 2026Article
- Direct Targeted Degradation of Transposon RNAs by the Non-Canonical RNAi Pathway of the FungusInternational journal of molecular sciences · 2025Article
- Stick-slip unfolding favors self-association of expanded HTT mRNA.Nature communications · 2024Article
- Context-dependent structure formation of hairpin motifs in bacteriophage MS2 genomic RNA.Biophysical journal · 2024Article
- Stick-slip unfolding favors self-association of expandedbioRxiv : the preprint server for biology · 2024Article
- CAG-Repeat RNA Hairpin Folding and Recruitment to Nuclear Speckles with a Pivotal Role of ATP as a Cosolute.Journal of the American Chemical Society · 2023Article
- G-Quadruplexes in Repeat Expansion Disorders.International journal of molecular sciences · 2023Review
- A probableHGG advances · 2022Article
- Targeting RNA structures with small molecules.Nature reviews. Drug discovery · 2022Review
- A Structural Potential of Rare Trinucleotide Repeat Tracts in RNA.International journal of molecular sciences · 2022Article
- Oligonucleotides Targeting DNA Repeats DownregulateNucleic acid therapeutics · 2021Article
- Ribonuclease recruitment using a small molecule reduced c9ALS/FTD r(GScience translational medicine · 2021Article
- SHAPE Directed Discovery of New Functions in Large RNAs.Accounts of chemical research · 2021Review
- The global and local distribution of RNA structure throughout the SARS-CoV-2 genome.Journal of virology · 2021Article
- The Contribution of Somatic Expansion of the CAG Repeat to Symptomatic Development in Huntington's Disease: A Historical Perspective.Journal of Huntington's disease · 2021Review
- DNA Repair in Huntington's Disease and Spinocerebellar Ataxias: Somatic Instability and Alternative Hypotheses.Journal of Huntington's disease · 2021Review
- A genetic association study of glutamine-encoding DNA sequence structures, somatic CAG expansion, and DNA repair gene variants, with Huntington disease clinical outcomes.EBioMedicine · 2019Article
- Expanded CUG repeats inRNA (New York, N.Y.) · 2019Article
- Design of Bivalent Nucleic Acid Ligands for Recognition of RNA-Repeated Expansion Associated with Huntington's Disease.Biochemistry · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The length of the CAG-repeat region in the huntingtin mRNA is predictive of Huntington's disease. Structural studies of CAG-repeat-containing RNAs suggest that these sequences form simple hairpin structures; however, in the context of the full-length huntingtin mRNA, CAG repeats may form complex structures that could be targeted for therapeutic intervention. We examined the structures of transcripts spanning the first exon of the huntingtin mRNA with both healthy and disease-prone repeat lengths. In transcripts with 17-70 repeats, the CAG sequences base paired extensively with nucleotides in the 5' UTR and with conserved downstream sequences including a CCG-repeat region. In huntingtin transcripts with healthy numbers of repeats, the previously observed CAG hairpin was either absent or short. In contrast, in transcripts with disease-associated numbers of repeats, a CAG hairpin was present and extended from a three-helix junction. Our findings demonstrate the profound importance of sequence context in RNA folding and identify specific structural differences between healthy and disease-inducing huntingtin alleles that may be targets for therapeutic intervention.
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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.