ArticleGenome biology2020
Purifying selection of long dsRNA is the first line of defense against false activation of innate immunity.
Article in Genome biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- dsRNAscan maps human dsRNAome, revealing conservation, intermolecular dsRNA, and correlates of ADAR dependency.Molecular cell · 2026Article
- Distinguishing self from non-self RNA by editing-specific inosine patterns.Nucleic acids research · 2026Article
- A cytoplasmic index for quantifying immune-related A-to-I RNA editing.Genome biology · 2026Article
- A transcriptome-wide systematic search does not detect A-to-I RNA editing inGenome research · 2026Article
- ADAR1 and ADAR2 associate with the RNA exosome and modulate RNA stability.Nucleic acids research · 2026Article
- Defects in intron recycling suppress the antiviral response via a mechanism of intronic endogenous dsRNA.The Journal of experimental medicine · 2026Article
- ADAR1 regulates dsRNA formation in nuclear and mitochondrial transcripts through editing-dependent and -independent mechanisms.Cell reports · 2026Article
- Adaptation of plateau frog peptide: From antimicrobial to angiogenic and proliferative functions.Journal of advanced research · 2026Article
- Comprehensive analysis of Saccharomyces cerevisiae intron structures in vivo.Nature structural & molecular biology · 2025Article
- Comprehensive Mapping of Human dsRNAome Reveals Conservation, Neuronal Enrichment, and Intermolecular Interactions.bioRxiv : the preprint server for biology · 2025Article
- REDIportal: toward an integrated view of the A-to-I editing.Nucleic acids research · 2025Article
- Gene silencing in the aedine cell lines C6/36 and U4.4 using long double-stranded RNA.Parasites & vectors · 2024Article
- Navigating the landscape of epitranscriptomics and host immunity.Genome research · 2024Review
- Novel insights into double-stranded RNA-mediated immunopathology.Nature reviews. Immunology · 2024Review
- The competitive landscape of the dsRNA world.Molecular cell · 2024Review
- Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes.Cell metabolism · 2024Article
- dsRID: in silico identification of dsRNA regions using long-read RNA-seq data.Bioinformatics (Oxford, England) · 2023Article
- Signature selection forces and evolutionary divergence of immune-survival genes compared between two important shrimp species.PloS one · 2023Article
- Site-directed RNA editing by harnessing ADARs: advances and challenges.Functional & integrative genomics · 2022Review
- Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
backgroundMobile elements comprise a large fraction of metazoan genomes. Accumulation of mobile elements is bound to produce multiple putative double-stranded RNA (dsRNA) structures within the transcriptome. These endogenous dsRNA structures resemble viral RNA and may trigger false activation of the innate immune response, leading to severe damage to the host cell. Adenosine to inosine (A-to-I) RNA editing is a common post-transcriptional modification, abundant within repetitive elements of all metazoans. It was recently shown that a key function of A-to-I RNA editing by ADAR1 is to suppress the immunogenic response by endogenous dsRNAs.
resultsHere, we analyze the transcriptomes of dozens of species across the Metazoa and identify a strong genomic selection against endogenous dsRNAs, resulting in their purification from the canonical transcriptome. This purifying selection is especially strong for long and nearly perfect dsRNAs. These are almost absent from mRNAs, but not pre-mRNAs, supporting the notion of selection due to cytoplasmic processes. The few long and nearly perfect structures found in human transcripts are weakly expressed and often heavily edited.
conclusionPurifying selection of long dsRNA is an important defense mechanism against false activation of innate immunity. This newly identified principle governs the integration of mobile elements into the genome, a major driving force of genome evolution. Furthermore, we find that most ADAR1 activity is not required to prevent an immune response to endogenous dsRNAs. The critical targets of ADAR1 editing are, likely, to be found mostly in non-canonical transcripts.
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