ArticleThe Journal of biological chemistry2014
The RNA-binding protein TDP-43 selectively disrupts microRNA-1/206 incorporation into the RNA-induced silencing complex.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Reprogramming heart failure: physiological orchestration and mechanistic decoding of exercise benefits.BMC cardiovascular disorders · 2025Pooled it
- MicroRNAs and Long Non-Coding RNAs Affect the Mechanisms Involved in Age-Related Neurodegeneration in a Manner Depending on RNA-Binding Proteins.Molecular neurobiology · 2026Review
- Beyond motor neurons: peripheral TDP-43 pathology in skeletal muscle and intramuscular nerves in amyotrophic lateral sclerosis.Brain communications · 2026Review
- Dicer Is Involved in Cytotoxicity and Motor Impairment Induced by TBPH Deficiency.Current issues in molecular biology · 2025Article
- Epigenetics in the formation of pathological aggregates in amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2024Review
- The Impact of Dysregulated microRNA Biogenesis Machinery and microRNA Sorting on Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- Implications of miRNAs dysregulation in amyotrophic lateral sclerosis: Challenging for clinical applications.Frontiers in neuroscience · 2023Review
- TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis.Translational neurodegeneration · 2022Review
- MiR-206 improves intervertebral disk degeneration by targeting GJA1.Journal of orthopaedic surgery and research · 2022Article
- Expanding the TDP-43 Proteinopathy Pathway From Neurons to Muscle: Physiological and Pathophysiological Functions.Frontiers in neuroscience · 2022Review
- RNA Deregulation in Amyotrophic Lateral Sclerosis: The Noncoding Perspective.International journal of molecular sciences · 2021Review
- Interplay of RNA-Binding Proteins and microRNAs in Neurodegenerative Diseases.International journal of molecular sciences · 2021Review
- TDP-43 aggregation induced by oxidative stress causes global mitochondrial imbalance in ALS.Nature structural & molecular biology · 2021Article
- Amyotrophic Lateral Sclerosis Genes inInternational journal of molecular sciences · 2021Review
- Trends in Understanding the Pathological Roles of TDP-43 and FUS Proteins.Advances in experimental medicine and biology · 2021Article
- The Regulatory Role of RNA Metabolism Regulator TDP-43 in Human Cancer.Frontiers in oncology · 2021Review
- BraInMap Elucidates the Macromolecular Connectivity Landscape of Mammalian Brain.Cell systems · 2020Article
- Role of RNA Binding Proteins with prion-like domains in muscle and neuromuscular diseases.Cell stress · 2020Review
- MicroRNAs: From Mechanism to Organism.Frontiers in cell and developmental biology · 2020Review
- Cytoplasmic TDP43 Binds microRNAs: New Disease Targets in Amyotrophic Lateral Sclerosis.Frontiers in cellular neuroscience · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
MicroRNA (miRNA) maturation is regulated by interaction of particular miRNA precursors with specific RNA-binding proteins. Following their biogenesis, mature miRNAs are incorporated into the RNA-induced silencing complex (RISC) where they interact with mRNAs to negatively regulate protein production. However, little is known about how mature miRNAs are regulated at the level of their activity. To address this, we screened for proteins differentially bound to the mature form of the miR-1 or miR-133 miRNA families. These muscle-enriched, co-transcribed miRNA pairs cooperate to suppress smooth muscle gene expression in the heart. However, they also have opposing roles, with the miR-1 family, composed of miR-1 and miR-206, promoting myogenic differentiation, whereas miR-133 maintains the progenitor state. Here, we describe a physical interaction between TDP-43, an RNA-binding protein that forms aggregates in the neuromuscular disease, amyotrophic lateral sclerosis, and the miR-1, but not miR-133, family. Deficiency of the TDP-43 Drosophila ortholog enhanced dmiR-1 activity in vivo. In mammalian cells, TDP-43 limited the activity of both miR-1 and miR-206, but not the miR-133 family, by disrupting their RISC association. Consistent with TDP-43 dampening miR-1/206 activity, protein levels of the miR-1/206 targets, IGF-1 and HDAC4, were elevated in TDP-43 transgenic mouse muscle. This occurred without corresponding Igf-1 or Hdac4 mRNA increases and despite higher miR-1 and miR-206 expression. Our findings reveal that TDP-43 negatively regulates the activity of the miR-1 family of miRNAs by limiting their bioavailability for RISC loading and suggest a processing-independent mechanism for differential regulation of miRNA activity.
Indexed as
Identifiers
What OpenQuestion holds
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.