ArticleBiochemistry2015
Crystallographic and Computational Analyses of AUUCU Repeating RNA That Causes Spinocerebellar Ataxia Type 10 (SCA10).
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions.Cells · 2022Review
- RNA toxicity in non-coding repeat expansion disorders.The EMBO journal · 2020Review
- The changing paradigm of intron retention: regulation, ramifications and recipes.Nucleic acids research · 2019Review
- Short Tandem Repeat Expansions and RNA-Mediated Pathogenesis in Myotonic Dystrophy.International journal of molecular sciences · 2019Review
- Intron retention induced by microsatellite expansions as a disease biomarker.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Protein sequestration as a normal function of long noncoding RNAs and a pathogenic mechanism of RNAs containing nucleotide repeat expansions.Human genetics · 2017Review
- RNA biology of disease-associated microsatellite repeat expansions.Acta neuropathologica communications · 2017Review
- RNA toxicity and foci formation in microsatellite expansion diseases.Current opinion in genetics & development · 2017Review
- Structural Characteristics of Simple RNA Repeats Associated with Disease and their Deleterious Protein Interactions.Frontiers in cellular neuroscience · 2017Review
- Controlled dehydration improves the diffraction quality of two RNA crystals.BMC structural biology · 2016Article
- Thermodynamic properties of water molecules in the presence of cosolute depend on DNA structure: a study using grid inhomogeneous solvation theory.Nucleic acids research · 2015Article
- Repeat-associated RNA structure and aberrant splicing.Biochimica et biophysica acta. Gene regulatory mechanismsReview
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Spinocerebellar ataxia type 10 (SCA10) is caused by a pentanucleotide repeat expansion of r(AUUCU) within intron 9 of the ATXN10 pre-mRNA. The RNA causes disease by a gain-of-function mechanism in which it inactivates proteins involved in RNA biogenesis. Spectroscopic studies showed that r(AUUCU) repeats form a hairpin structure; however, there were no high-resolution structural models prior to this work. Herein, we report the first crystal structure of model r(AUUCU) repeats refined to 2.8 Å and analysis of the structure via molecular dynamics simulations. The r(AUUCU) tracts adopt an overall A-form geometry in which 3 × 3 nucleotide (5')UCU(3')/(3')UCU(5') internal loops are closed by AU pairs. Helical parameters of the refined structure as well as the corresponding electron density map on the crystallographic model reflect dynamic features of the internal loop. The computational analyses captured dynamic motion of the loop closing pairs, which can form single-stranded conformations with relatively low energies. Overall, the results presented here suggest the possibility for r(AUUCU) repeats to form metastable A-from structures, which can rearrange into single-stranded conformations and attract proteins such as heterogeneous nuclear ribonucleoprotein K (hnRNP K). The information presented here may aid in the rational design of therapeutics targeting this RNA.
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Registered trials
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