ArticleNature communications2024
Stick-slip unfolding favors self-association of expanded HTT mRNA.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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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.
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Who cites it
3 citing papers in PubMed.
- Single-Molecule Dwell Times in Biomolecular Condensates.bioRxiv : the preprint server for biology · 2026Article
- Characterization of RNA Structure Dynamics with Trans-Factors Using Single-Molecule Optical Tweezers.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Nucleotide-Specific RNA Conformations and Dynamics as Precursors to Ribonucleoprotein Condensates.Journal of the American Chemical Society · 2025Article
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Authors and funding
6 authors.
Funding
Abstract
In Huntington's Disease (HD) and related disorders, expansion of CAG trinucleotide repeats produces a toxic gain of function in affected neurons. Expanded huntingtin (expHTT) mRNA forms aggregates that sequester essential RNA binding proteins, dysregulating mRNA processing and translation. The physical basis of RNA aggregation has been difficult to disentangle owing to the heterogeneous structure of the CAG repeats. Here, we probe the folding and unfolding pathways of expHTT mRNA using single-molecule force spectroscopy. Whereas normal HTT mRNAs unfold reversibly and cooperatively, expHTT mRNAs with 20 or 40 CAG repeats slip and unravel non-cooperatively at low tension. Slippage of CAG base pairs is punctuated by concerted rearrangement of adjacent CCG trinucleotides, trapping partially folded structures that readily base pair with another RNA strand. We suggest that the conformational entropy of the CAG repeats, combined with stable CCG base pairs, creates a stick-slip behavior that explains the aggregation propensity of expHTT mRNA.
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Registered trials
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