ArticleScience translational medicine2016
Loss-of-function mutations in the RNA biogenesis factor NAF1 predispose to pulmonary fibrosis-emphysema.
Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 3 of them syntheses that pooled it.
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Who cites it
128 citing papers in PubMed, 3 syntheses or guidelines pooled it, 203 citations in OpenAlex.
- Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes.Nature communications · 2024Pooled it
- Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.Nature communications · 2023Pooled it
- Guideline
- Telomere Length and Use of Immunosuppressive Medications in Idiopathic Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2019Trial
- Telomere-associated non-malignant pulmonary diseases: Pathogenic mechanisms and therapeutic strategies.Acta pharmaceutica Sinica. B · 2026Review
- Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease.Physiological reviews · 2026Review
- Identification of circadian rhythm-related genes in colorectal cancer by integrating bioinformatics and multi-omics mendelian randomization.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Advances in our understanding of distal progenitors in idiopathic pulmonary fibrosis: implications for novel therapeutics.The European respiratory journal · 2026Review
- Clonal Signatures of Telomere Biology Disorders.Current hematologic malignancy reports · 2026Review
- Efficient CRISPR-Cas RNP-based gene targeting of human AT2 cells.American journal of respiratory cell and molecular biology · 2026Article
- Idiopathic Pulmonary Fibrosis: A Comprehensive Review of Risk Factors, Genetics, Diagnosis, and Therapeutic Approaches.Biomedicines · 2026Review
- Genetic Familial Interstitial Lung Disease.Clinics in chest medicine · 2025Review
- Hydronidone Mitigates Pulmonary Fibrosis by Regulating the TGF-β/Smad2/3 Axis inACS pharmacology & translational science · 2025Article
- A tiered strategy to identify relevant genetic variants in familial pulmonary fibrosis: a proof of concept for the clinical practice.European journal of human genetics : EJHG · 2025Article
- Mendelian causes of early-onset emphysema: a review of the current literature.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Integrated bioinformatics and machine learning reveal key genes and immune mechanisms associated with uremia.Scientific reports · 2025Article
- Telomere function and regulation from mouse models to human ageing and disease.Nature reviews. Molecular cell biology · 2025Review
- Viewpoint: Pre- and post-lung transplant considerations for patients with ultra-short telomere length.The European respiratory journal · 2025Article
- Progressive lung fibrosis: reprogramming a genetically vulnerable bronchoalveolar epithelium.The Journal of clinical investigation · 2025Review
- Hematological complications in solid organ transplant recipients with telomere biology disorders: a narrative review.Frontiers in immunology · 2025Review
68 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Chronic obstructive pulmonary disease and pulmonary fibrosis have been hypothesized to represent premature aging phenotypes. At times, they cluster in families, but the genetic basis is not understood. We identified rare, frameshift mutations in the gene for nuclear assembly factor 1, NAF1, a box H/ACA RNA biogenesis factor, in pulmonary fibrosis-emphysema patients. The mutations segregated with short telomere length, low telomerase RNA levels, and extrapulmonary manifestations including myelodysplastic syndrome and liver disease. A truncated NAF1 was detected in cells derived from patients, and, in cells in which the frameshift mutation was introduced by genome editing, telomerase RNA levels were reduced. The mutant NAF1 lacked a conserved carboxyl-terminal motif, which we show is required for nuclear localization. To understand the disease mechanism, we used CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein-9 nuclease) to generate Naf1(+/-) mice and found that they had half the levels of telomerase RNA. Other box H/ACA RNA levels were also decreased, but rRNA pseudouridylation, which is guided by snoRNAs, was intact. Moreover, first-generation Naf1(+/-) mice showed no evidence of ribosomal pathology. Our data indicate that disease in NAF1 mutation carriers is telomere-mediated; they show that NAF1 haploinsufficiency selectively disturbs telomere length homeostasis by decreasing the levels of telomerase RNA while sparing rRNA pseudouridylation.
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