ArticleNature2013
Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01353430 (Characterization of Familial Myopathy and Paget Disease of Bone), which is not on this map. Cited by 926 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.
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.
Characterization of Familial Myopathy and Paget Disease of Bone
Who cites it
926 citing papers in PubMed, 1,475 citations in OpenAlex.
- Mechanistic studies on HNRNPA2B1 suggest binding but not selective recognition of mRNA biology · 2026Article
- RNA G-quadruplex-protein interactions: from nuclear RNA processing to cytoplasmic stress response and neurodegeneration.RNA biology · 2026Review
- How do low-complexity domain interactions control transcription?Biochemical Society transactions · 2026Review
- Assessment of Aggregation- and Condensation-Prone Regions of Proteins Involved in Neurodegenerative, Neurological and Mental-State Diseases.Biomolecules · 2026Article
- Beyond the structure-function paradigm: A comprehensive review of intrinsically disordered proteins.Biochemistry and biophysics reports · 2026Review
- FUS controls muscle differentiation through phase separation-mediated recruitment of the transcription factors MEF2 and ETV5.The EMBO journal · 2026Article
- YTHDC1 functions as a molecular chaperone to suppress ALS-linked hnRNPA1 mutants from aggregation.Nature communications · 2026Article
- Neurodegenerative-related gene rescue in anterior insula after early life maltreatment restores adult social interaction in male mice.Molecular psychiatry · 2026Article
- Inhibition and Formation of Amyloid Fibrils in the Bulk and at the Interface of Biomolecular Condensates.Angewandte Chemie (International ed. in English) · 2026Review
- HNRNPD Induces Radioresistance in Nasopharyngeal Carcinoma by Sequestering GRAMD4 mRNA in Stress Granules.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ensemble Docking and Molecular Dynamics Indicate Dynamic Modulation of hnRNPA1 UP1 Interdomain Behavior by Natural Products.ACS omega · 2026Article
- Impaired Myogenic Differentiation Is a Shared Feature Across Genetic Myopathies.International journal of molecular sciences · 2026Review
- HnRNPA2B1 tunes antimycobacterial immune responses in macrophages through alternative splicing ofInfection and immunity · 2026Article
- Expansion of the Clinical and Genetic Spectra of hnRNPA1-Associated Distal Myopathy in Two Korean Families.Journal of clinical neurology (Seoul, Korea) · 2026Article
- Isoform-specific steric zippers drive aberrant assembly and mislocalization of shortened TDP-43.Science advances · 2026Article
- Dysregulation of liquid-liquid phase separation: from molecular mechanisms to targeted therapies in cardiovascular diseases.Journal of nanobiotechnology · 2026Review
- Upregulated PKM2 Protects Dopaminergic Neurons From Oxidative Damage Through Nrf2 Transactivation in an MPTP-Induced Mouse Model of Parkinson's Disease.CNS neuroscience & therapeutics · 2026Article
- Ligand-specific conformational dynamics and interaction landscapes of hnRNPA2B1 reveal a structural basis for its functional regulation.Current research in structural biology · 2026Article
- Article
- RNA-binding protein hnRNPK: a multifunctional regulator of skeletal muscle biology and disease.Biochemical Society transactions · 2026Review
866 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
37 authors at 16 institutions in 3 countries.
Funding
Abstract
Algorithms designed to identify canonical yeast prions predict that around 250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbour a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here we define pathogenic mutations in PrLDs of heterogeneous nuclear ribonucleoproteins (hnRNPs) A2B1 and A1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and in one case of familial amyotrophic lateral sclerosis. Wild-type hnRNPA2 (the most abundant isoform of hnRNPA2B1) and hnRNPA1 show an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a 'steric zipper' motif in the PrLD, which accelerates the formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Notably, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant steric zipper motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs should therefore be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone.
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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.