ReviewPLoS genetics2021
To "Z" or not to "Z": Z-RNA, self-recognition, and the MDA5 helicase.
Review in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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
35 citing papers in PubMed.
- ZBP1 specifically binds pre-formed Z-RNA, limiting its potential pool of nucleic acid ligands compared to ADAR1.Nucleic acids research · 2026Article
- Targeting ADAR1 p150 triggers tumor inhibition and antitumor immunity to overcome immunotherapy resistance.iScience · 2026Article
- Zα and Zβ domains of ADAR1 and ZBP1 bind G-quadruplexes with nanomolar affinities, establishing Zβ as a G-quadruplex-specific domain.Nucleic acids research · 2026Article
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Identification of ADAR1i-124: The first effective A-to-I RNA editing inhibitor with promising cancer therapeutic potential.iScience · 2026Article
- MYC drives left-handed Z-DNA formation to shape gene expression.Nature communications · 2025Article
- Leveraging genetics to understand ADAR1-mediated RNA editing in health and disease.Nature reviews. Genetics · 2025Review
- Triplexes Color the Chromaverse by Modulating Nucleosome Phasing and Anchoring Chromatin Condensates.International journal of molecular sciences · 2025Review
- Zα and Zβ Localize ADAR1 to Flipons That Modulate Innate Immunity, Alternative Splicing, and Nonsynonymous RNA Editing.International journal of molecular sciences · 2025Review
- Flipons enable genomes to learn by intermediating the exchange of energy for information.Journal of the Royal Society, Interface · 2025Review
- The Flipons, Infections, and Amyloids that Foreshadow the Fading Memories of Alzheimer's Disease.Neuroscience insights · 2025Review
- Osteogenesis imperfecta type 10 and the cellular scaffolds underlying common immunological diseases.Genes and immunity · 2024Review
- The role of DNA in the pathogenesis of SLE: DNA as a molecular chameleon.Annals of the rheumatic diseases · 2024Review
- The ancient Z-DNA and Z-RNA specific Zα fold has evolved modern roles in immunity and transcription through the natural selection of flipons.Royal Society open science · 2024Article
- Adenosine deaminases that act on RNA, then and now.RNA (New York, N.Y.) · 2024Article
- Structurally Specific Z-DNA Proteolysis Targeting Chimera Enables Targeted Degradation of Adenosine Deaminase Acting on RNA 1.Journal of the American Chemical Society · 2024Article
- Article
- Z-Form Adoption of Nucleic Acid is a Multi-Step Process Which Proceeds through a Melted Intermediate.Journal of the American Chemical Society · 2024Article
- The competitive landscape of the dsRNA world.Molecular cell · 2024Review
- Neurodegenerative diseases reflect the reciprocal roles played by retroelements in regulating memory and immunity.Frontiers in neuroscience · 2024Article
Corrections and comments
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Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Double-stranded RNA (dsRNA) is produced both by virus and host. Its recognition by the melanoma differentiation-associated gene 5 (MDA5) initiates type I interferon responses. How can a host distinguish self-transcripts from nonself to ensure that responses are targeted correctly? Here, I discuss a role for MDA5 helicase in inducing Z-RNA formation by Alu inverted repeat (AIR) elements. These retroelements have highly conserved sequences that favor Z-formation, creating a site for the dsRNA-specific deaminase enzyme ADAR1 to dock. The subsequent editing destabilizes the dsRNA, ending further interaction with MDA5 and terminating innate immune responses directed against self. By enabling self-recognition, Alu retrotransposons, once invaders, now are genetic elements that keep immune responses in check. I also discuss the possible but less characterized roles of the other helicases in modulating innate immune responses, focusing on DExH-box helicase 9 (DHX9) and Mov10 RISC complex RNA helicase (MOV10). DHX9 and MOV10 function differently from MDA5, but still use nucleic acid structure, rather than nucleotide sequence, to define self. Those genetic elements encoding the alternative conformations involved, referred to as flipons, enable helicases to dynamically shape a cell's repertoire of responses. In the case of MDA5, Alu flipons switch off the dsRNA-dependent responses against self. I suggest a number of genetic systems in which to study interactions between flipons and helicases further.
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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.