ArticleImmunity2024
Lysosomal endonuclease RNase T2 and PLD exonucleases cooperatively generate RNA ligands for TLR7 activation.
Article in Immunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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
29 citing papers in PubMed.
- TLR7 in systemic lupus erythematosus: genetics and emerging therapies.Nature reviews. Rheumatology · 2026Review
- Phagocytosis: a process that shapes immune responses to engulfed meals.Nature reviews. Immunology · 2026Review
- An inhibitory RNA checkpoint in TLR7 and TLR8.Nature immunology · 2026Article
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- Innate immune recognition and evasion strategies of hepatitis B virus: from DNA to RNA and viral proteins.Frontiers in immunology · 2026Review
- Renal macrophage TLR7 signaling in lupus nephritis: from pathogenic mechanisms to therapeutic opportunities.Frontiers in immunology · 2026Review
- Phospholipase D: emerging therapeutic targets in signaling, metabolism, and immune-oncology.Cell communication and signaling : CCS · 2025Review
- Mechanistic insights into single-stranded DNA degradation by lysosomal exonucleases PLD3 and PLD4 from structural snapshots.Nature communications · 2025Article
- The lysosomal catabolism of nucleic acids-critical regulators of the innate immune system.Nucleic acids research · 2025Review
- Dendritic Cells: Origin, Classification, Development, Biological Functions, and Therapeutic Potential.MedComm · 2025Review
- Article
- Two-pronged immune evasion of pseudouridine-modified RNA.Trends in molecular medicine · 2025Article
- Lysosomal RNA profiling reveals targeting of specific types of RNAs for degradation.bioRxiv : the preprint server for biology · 2025Article
- For "U" the bell tolls: Pseudouridine evades TLR detection.Molecular cell · 2025Article
- Single-Cell mRNA Analysis for the Identification of Molecular Pathways of IRF1 in HER2+ Breast Cancer.Cells · 2025Article
- Innate immune responses to lysosomal nucleic acid stress.Journal of biochemistry · 2025Review
- Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms.Journal of biomedical science · 2025Review
- From Rare to Common: Genetic Insights into TLR7 Variants in a Multicentric Spanish Study on COVID-19 Severity.Journal of clinical immunology · 2025Article
- Small RNA and Toll-like receptor interactions: origins and disease mechanisms.Trends in biochemical sciences · 2025Review
- Nucleic acid triggers of autoimmunity and autoinflammation.Current opinion in immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor 7 (TLR7) is essential for recognition of RNA viruses and initiation of antiviral immunity. TLR7 contains two ligand-binding pockets that recognize different RNA degradation products: pocket 1 recognizes guanosine, while pocket 2 coordinates pyrimidine-rich RNA fragments. We found that the endonuclease RNase T2, along with 5' exonucleases PLD3 and PLD4, collaboratively generate the ligands for TLR7. Specifically, RNase T2 generated guanosine 2',3'-cyclic monophosphate-terminated RNA fragments. PLD exonuclease activity further released the terminal 2',3'-cyclic guanosine monophosphate (2',3'-cGMP) to engage pocket 1 and was also needed to generate RNA fragments for pocket 2. Loss-of-function studies in cell lines and primary cells confirmed the critical requirement for PLD activity. Biochemical and structural studies showed that PLD enzymes form homodimers with two ligand-binding sites important for activity. Previously identified disease-associated PLD mutants failed to form stable dimers. Together, our data provide a mechanistic basis for the detection of RNA fragments by TLR7.
Indexed as
Identifiers
What Socratic 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 Socratic graph.