ArticleThe Journal of clinical investigation2015
Poly(A)-specific ribonuclease deficiency impacts telomere biology and causes dyskeratosis congenita.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
127 citing papers in PubMed, 1 synthesis or guideline pooled it, 196 citations in OpenAlex.
- Pulmonary fibrosis in dyskeratosis congenita: a case report with a PRISMA-compliant systematic review.BMC pulmonary medicine · 2021Pooled it
- Investigation of chromosome X inactivation and clinical phenotypes in female carriers of DKC1 mutations.American journal of hematology · 2016Trial
- Genetic influences on haematopoiesis.Nature reviews. Genetics · 2026Review
- Mutual feedback regulation between Poly(A)-specific ribonuclease (PARN) and cognate microRNAs.Life science alliance · 2026Article
- Clonal Signatures of Telomere Biology Disorders.Current hematologic malignancy reports · 2026Review
- Biogenesis and Regulation of Telomerase during Development and Cancer.Cold Spring Harbor perspectives in biology · 2026Review
- Exosome-mediated decay of unstable long extended precursors of human telomerase RNA is dependent on 5'-cap trimethylation.Genes & development · 2026Article
- Monoallelic PARN mutation presenting as pancytopenia, hepatic fibrosis and idiopathic pulmonary fibrosis.BMJ case reports · 2026Article
- The Impact of Genetics on Pediatric Interstitial Lung Diseases: A Narrative Literature Review and Clinical Implications.Biomedicines · 2026Review
- RNA Analysis Uncovers Pathogenic PARN Variant in Dyskeratosis Congenita.Clinical genetics · 2026Article
- Ribonucleases in Mendelian disease: Characterization and insight from model organisms.Genes & diseases · 2025Review
- Germline PARN Variants in Telomere Biology Disorders and Challenges in Variant Curation.Molecular genetics & genomic medicine · 2025Article
- Fine Regulation of MicroRNAs in Gene Regulatory Networks and Pathophysiology.International journal of molecular sciences · 2025Review
- Hematological complications in solid organ transplant recipients with telomere biology disorders: a narrative review.Frontiers in immunology · 2025Review
- Optical Genomic Mapping and Next-Generation Sequencing Identified Retrotransposon Insertion and Missense Variant DisruptingHuman mutation · 2025Article
- Hoyeraal-Hreidarsson syndrome: a case report of dyskeratosis congenita with a novel PARN gene mutation.Annals of medicine and surgery (2012) · 2024Article
- The evolving genetic landscape of telomere biology disorder dyskeratosis congenita.EMBO molecular medicine · 2024Article
- Inherited Telomere Biology Disorders: Pathophysiology, Clinical Presentation, Diagnostics, and Treatment.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2024Review
- Sm complex assembly and 5' cap trimethylation promote selective processing of snRNAs by the 3' exonuclease TOE1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Comprehensive Treatment and Gene Analysis of a Male Patient with Follicular Occlusion Tetrad with Fordyce Granules.Clinical, cosmetic and investigational dermatology · 2024Article
67 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Dyskeratosis congenita (DC) and related syndromes are inherited, life-threatening bone marrow (BM) failure disorders, and approximately 40% of cases are currently uncharacterized at the genetic level. Here, using whole exome sequencing (WES), we have identified biallelic mutations in the gene encoding poly(A)-specific ribonuclease (PARN) in 3 families with individuals exhibiting severe DC. PARN is an extensively characterized exonuclease with deadenylation activity that controls mRNA stability in part and therefore regulates expression of a large number of genes. The DC-associated mutations identified affect key domains within the protein, and evaluation of patient cells revealed reduced deadenylation activity. This deadenylation deficiency caused an early DNA damage response in terms of nuclear p53 regulation, cell-cycle arrest, and reduced cell viability upon UV treatment. Individuals with biallelic PARN mutations and PARN-depleted cells exhibited reduced RNA levels for several key genes that are associated with telomere biology, specifically TERC, DKC1, RTEL1, and TERF1. Moreover, PARN-deficient cells also possessed critically short telomeres. Collectively, these results identify a role for PARN in telomere maintenance and demonstrate that it is a disease-causing gene in a subset of patients with severe DC.
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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.