ArticleNature communications2019
A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation.
Article in Nature communications, 2019. 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 40 papers.
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Who cites it
40 citing papers in PubMed, 62 citations in OpenAlex.
- Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency.The Journal of allergy and clinical immunology · 2021Trial
- Proximity labeling puts ZFP36L1 as central hub for posttranscriptional regulation networks in T cells.Life science alliance · 2026Article
- Targeting T follicular helper cells for lifelong health.Nature reviews. Drug discovery · 2026Review
- RNA-binding proteins and ribonucleoproteins as determinants of immunity.Nature reviews. Immunology · 2026Review
- Widespread prevalence of CD19 exon 5-6 skipping in primary pediatric B-Cell acute lymphoblastic leukemia patients.Molecular and cellular pediatrics · 2025Article
- Plans within plans: post-transcriptional regulation governs macrophage responses.Trends in immunology · 2025Review
- Biomolecular condensates in immune cell fate.Nature reviews. Immunology · 2025Review
- Deep insight into cytokine storm: from pathogenesis to treatment.Signal transduction and targeted therapy · 2025Review
- Modulation of host gene expression by the zinc finger antiviral protein.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Stem Loop Mediated Transgene Modulation in Human T Cells.ACS synthetic biology · 2024Article
- Bioinformatic Analysis of Roquin Family Reveals Their Potential Role in Immune System.International journal of molecular sciences · 2024Article
- Regulation of inflammatory diseases via the control of mRNA decay.Inflammation and regeneration · 2024Review
- The thymocyte-specific RNA-binding protein Arpp21 provides TCR repertoire diversity by binding to the 3'-UTR and promoting Rag1 mRNA expression.Nature communications · 2024Article
- Late Onset of Primary Hemophagocytic Lymphohistiocytosis (HLH) with a Novel Constellation of Compound Heterozygosity Involving Two Missense Variants in theInternational journal of molecular sciences · 2024Review
- ZFP36 disruption is insufficient to enhance the function of mesothelin-targeting human CAR-T cells.Scientific reports · 2024Article
- Inborn Errors of Immunity and Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- RNA Metabolism Governs Immune Function and Response.Advances in experimental medicine and biology · 2024Review
- Unrestrained cleavage of Roquin-1 by MALT1 induces spontaneous T cell activation and the development of autoimmunity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- RNA circuits and RNA-binding proteins in T cells.Trends in immunology · 2023Review
- Roquin-1 resolves sepsis-associated acute liver injury by regulating inflammatory profiles via miRNA cargo in extracellular vesicles.iScience · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
28 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperinflammatory syndromes are life-threatening disorders caused by overzealous immune cell activation and cytokine release, often resulting from defects in negative feedback mechanisms. In the quintessential hyperinflammatory syndrome familial hemophagocytic lymphohistiocytosis (HLH), inborn errors of cytotoxicity result in effector cell accumulation, immune dysregulation and, if untreated, tissue damage and death. Here, we describe a human case with a homozygous nonsense R688* RC3H1 mutation suffering from hyperinflammation, presenting as relapsing HLH. RC3H1 encodes Roquin-1, a posttranscriptional repressor of immune-regulatory proteins such as ICOS, OX40 and TNF. Comparing the R688* variant with the murine M199R variant reveals a phenotypic resemblance, both in immune cell activation, hypercytokinemia and disease development. Mechanistically, R688* Roquin-1 fails to localize to P-bodies and interact with the CCR4-NOT deadenylation complex, impeding mRNA decay and dysregulating cytokine production. The results from this unique case suggest that impaired Roquin-1 function provokes hyperinflammation by a failure to quench immune activation.
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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.