ArticleProceedings of the National Academy of Sciences of the United States of America2012
Kinetic mechanism for viral dsRNA length discrimination by MDA5 filaments.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 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
119 citing papers in PubMed, 164 citations in OpenAlex.
- dsRNAscan maps human dsRNAome, revealing conservation, intermolecular dsRNA, and correlates of ADAR dependency.Molecular cell · 2026Article
- Establishing the molecular basis for MDA5 mutation-linked autoimmunity.Nucleic acids research · 2026Article
- Loss of cellular RNA homeostasis contributes to MDA5 activation during virus infection.Nature immunology · 2026Article
- The current landscape of mRNA therapy and the strategies for mRNA purification and dsRNA removal.Journal of biomedical science · 2026Review
- Lassa and Mopeia viruses produce different RIG-I-activating RNA in the absence of a functional viral exoribonuclease domain.Journal of virology · 2026Article
- Identification of highly immunogenic endogenous dsRNAs from cellular MDA5 filaments.bioRxiv : the preprint server for biology · 2026Article
- Trans-Kingdom dsRNA Sensing:bioRxiv : the preprint server for biology · 2026Article
- A transcriptome-wide systematic search does not detect A-to-I RNA editing inGenome research · 2026Article
- Structural and mechanistic basis of ADAR1-mediated RNA editing and immune regulation.Cell insight · 2026Review
- Sensing of double-stranded RNA in human cells: molecular mechanisms and cellular consequences.Biochemical Society transactions · 2026Review
- SS-VIME: a single-source virome-microbiome extraction protocol toward comprehensive soil community analysis.Microbiology spectrum · 2026Article
- MDA5 generates compact ribonucleoprotein complexes via ATP-dependent double-stranded RNA unwinding.Nucleic acids research · 2026Article
- Process and analytical strategies for the safe production of mRNA vaccines and therapeutics.Molecular biology reports · 2026Review
- Template nicking suppresses promoter-independent antisense transcription in IVT via R-loop-mediated strand displacement.Nucleic acids research · 2026Article
- Deciphering host-virus interaction networks in ALV infection: an integrative multi-omics perspective.Frontiers in immunology · 2026Review
- ADAR1 editing is necessary for only a small subset of cytosolic dsRNAs to evade MDA5-mediated autoimmunity.Nature genetics · 2025Article
- LGP2 stops MDA5 translocation to start antiviral signaling.Cell research · 2025Article
- ATP-dependent one-dimensional movement maintains immune homeostasis by suppressing spontaneous MDA5 filament assembly.Cell research · 2025Article
- A two-step mechanism for RIG-I activation by influenza virus mvRNAs.Science advances · 2025Article
- Leveraging genetics to understand ADAR1-mediated RNA editing in health and disease.Nature reviews. Genetics · 2025Review
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The viral sensor MDA5 distinguishes between cellular and viral dsRNAs by length-dependent recognition in the range of ~0.5-7 kb. The ability to discriminate dsRNA length at this scale sets MDA5 apart from other dsRNA receptors of the immune system. We have shown previously that MDA5 forms filaments along dsRNA that disassemble upon ATP hydrolysis. Here, we demonstrate that filament formation alone is insufficient to explain its length specificity, because the intrinsic affinity of MDA5 for dsRNA depends only moderately on dsRNA length. Instead, MDA5 uses a combination of end disassembly and slow nucleation kinetics to "discard" short dsRNA rapidly and to suppress rebinding. In contrast, filaments on long dsRNA cycle between partial end disassembly and elongation, bypassing nucleation steps. MDA5 further uses this repetitive cycle of assembly and disassembly processes to repair filament discontinuities, which often are present because of multiple, internal nucleation events, and to generate longer, continuous filaments that more accurately reflect the length of the underlying dsRNA scaffold. Because the length of the continuous filament determines the stability of the MDA5-dsRNA interaction, the mechanism proposed here provides an explanation for how MDA5 uses filament assembly and disassembly dynamics to discriminate between self vs. nonself dsRNA.
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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.