ArticlePLoS pathogens2014
Human genome-wide RNAi screen identifies an essential role for inositol pyrophosphates in Type-I interferon response.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 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
48 citing papers in PubMed, 76 citations in OpenAlex.
- Inositol pyrophosphate kinases in health and disease.FEBS letters · 2026Review
- Proteome-wide quantification of inositol pyrophosphate-protein interactions.Nature communications · 2026Article
- CRISPR with Transcriptional Readout reveals influenza transcription is modulated by NELF and can precipitate an interferon response.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting IGF2 to reprogram the tumor microenvironment for enhanced viro-immunotherapy.Neuro-oncology · 2024Article
- Functions, Mechanisms, and therapeutic applications of the inositol pyrophosphates 5PP-InsPJournal of cardiovascular translational research · 2024Review
- PPIP5K2 Facilitates Proliferation and Metastasis of Non-Small Lung Cancer (NSCLC) through AKT Signaling Pathway.Cancers · 2024Article
- Research Advances on Swine Acute Diarrhea Syndrome Coronavirus.Animals : an open access journal from MDPI · 2024Review
- Inositol Pyrophosphate-Controlled Kinetochore Architecture and Mitotic Entry inJournal of fungi (Basel, Switzerland) · 2022Article
- Review
- PPIP5K2 promotes colorectal carcinoma pathogenesis through facilitating DNA homologous recombination repair.Oncogene · 2021Article
- Echinacea purpurea (L.) Moench treatment of monocytes promotes tonic interferon signaling, increased innate immunity gene expression and DNA repeat hypermethylated silencing of endogenous retroviral sequences.BMC complementary medicine and therapies · 2021Article
- Analyses of Inositol Phosphates and Phosphoinositides by Strong Anion Exchange (SAX)-HPLC.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Article
- Metabolism and Functions of Inositol Pyrophosphates: Insights Gained from the Application of Synthetic Analogues.Molecules (Basel, Switzerland) · 2020Review
- The intersection between stress responses and inositol pyrophosphates in Saccharomyces cerevisiae.Current genetics · 2020Review
- Primate lentiviruses require Inositol hexakisphosphate (IP6) or inositol pentakisphosphate (IP5) for the production of viral particles.PLoS pathogens · 2020Article
- Inositol Pyrophosphates: Signaling Molecules with Pleiotropic Actions in Mammals.Molecules (Basel, Switzerland) · 2020Review
- Vip1 is a kinase and pyrophosphatase switch that regulates inositol diphosphate signaling.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Significant inhibition of re-emerged and emerging swine enteric coronavirus in vitro using the multiple shRNA expression vector.Antiviral research · 2019Article
- ADAR1: "Editor-in-Chief" of Cytoplasmic Innate Immunity.Frontiers in immunology · 2019Review
Corrections and comments
- Erratum issued
- Erratum issuedMcCaffrey, Kathleen [added]
Authors and funding
17 authors at 10 institutions in 4 countries.
Funding
Abstract
The pattern recognition receptor RIG-I is critical for Type-I interferon production. However, the global regulation of RIG-I signaling is only partially understood. Using a human genome-wide RNAi-screen, we identified 226 novel regulatory proteins of RIG-I mediated interferon-β production. Furthermore, the screen identified a metabolic pathway that synthesizes the inositol pyrophosphate 1-IP7 as a previously unrecognized positive regulator of interferon production. Detailed genetic and biochemical experiments demonstrated that the kinase activities of IPPK, PPIP5K1 and PPIP5K2 (which convert IP5 to1-IP7) were critical for both interferon induction, and the control of cellular infection by Sendai and influenza A viruses. Conversely, ectopically expressed inositol pyrophosphate-hydrolases DIPPs attenuated interferon transcription. Mechanistic experiments in intact cells revealed that the expression of IPPK, PPIP5K1 and PPIP5K2 was needed for the phosphorylation and activation of IRF3, a transcription factor for interferon. The addition of purified individual inositol pyrophosphates to a cell free reconstituted RIG-I signaling assay further identified 1-IP7 as an essential component required for IRF3 activation. The inositol pyrophosphate may act by β-phosphoryl transfer, since its action was not recapitulated by a synthetic phosphonoacetate analogue of 1-IP7. This study thus identified several novel regulators of RIG-I, and a new role for inositol pyrophosphates in augmenting innate immune responses to viral infection that may have therapeutic applications.
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.