ArticleBlood advances2020
Chemical inhibition of PAPD5/7 rescues telomerase function and hematopoiesis in dyskeratosis congenita.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Primer- and template-independent RNA polymerization by terminal nucleotidyltransferase TENT4B.Nucleic acids research · 2026Article
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- Bilateral Continuous Femoral Nerve Blocks as an Opioid-Sparing Strategy for Refractory Lower Extremity Pain in Adult Sickle Cell Crisis: A Case Report.Reports (MDPI) · 2026Article
- 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
- Diagnosis and management of adult telomere biology disorders.Haematologica · 2026Review
- Dyskerin dysfunction in cancer development: from telomere dysregulation to immune deficiency.American journal of cancer research · 2026Review
- Established and emerging non-cellular therapies in inherited bone marrow failure syndromes.Frontiers in immunology · 2026Review
- Extension of replicative lifespan by synthetic engineered telomerase RNA in patient induced pluripotent stem cells.Nature biomedical engineering · 2025Article
- Telomere Shortening in Interstitial Lung Disease: Challenges and Promises.The clinical respiratory journal · 2025Review
- Germline PARN Variants in Telomere Biology Disorders and Challenges in Variant Curation.Molecular genetics & genomic medicine · 2025Article
- The evolving genetic landscape of telomere biology disorder dyskeratosis congenita.EMBO molecular medicine · 2024Article
- RNA tailing machinery drives amyloidogenic phase transition.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Advances in understanding telomerase assembly.Biochemical Society transactions · 2023Review
- Pediatric Bone Marrow Failure: A Broad Landscape in Need of Personalized Management.Journal of clinical medicine · 2023Review
- TCAB1 prevents nucleolar accumulation of the telomerase RNA to facilitate telomerase assembly.Cell reports · 2023Article
- USB1 is a miRNA deadenylase that regulates hematopoietic development.Science (New York, N.Y.) · 2023Article
- Recent Progress in Cyclic Aryliodonium Chemistry: Syntheses and Applications.Chemical reviews · 2023Review
- A missense variant in the nuclear localization signal of DKC1 causes Hoyeraal-Hreidarsson syndrome.NPJ genomic medicine · 2022Article
- Telomere biology disorders: time for moving towards the clinic?Trends in molecular medicine · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Dyskeratosis congenita (DC) is a pediatric bone marrow failure syndrome caused by germline mutations in telomere biology genes. Mutations in DKC1 (the most commonly mutated gene in DC), the 3' region of TERC, and poly(A)-specific ribonuclease (PARN) cause reduced levels of the telomerase RNA component (TERC) by reducing its stability and accelerating TERC degradation. We have previously shown that depleting wild-type DKC1 levels by RNA interference or expression of the disease-associated A353V mutation in the DKC1 gene leads to decay of TERC, modulated by 3'-end oligoadenylation by noncanonical poly(A) polymerase 5 (PAPD5) followed by 3' to 5' degradation by EXOSC10. Furthermore, the constitutive genetic silencing of PAPD5 is sufficient to rescue TERC levels, restore telomerase function, and elongate telomeres in DKC1_A353V mutant human embryonic stem cells (hESCs). Here, we tested a novel PAPD5/7 inhibitor (RG7834), which was originally discovered in screens against hepatitis B viral loads in hepatic cells. We found that treatment with RG7834 rescues TERC levels, restores correct telomerase localization in DKC1 and PARN-depleted cells, and is sufficient to elongate telomeres in DKC1_A353V hESCs. Finally, treatment with RG7834 significantly improved definitive hematopoietic potential from DKC1_A353V hESCs, indicating that the chemical inhibition of PAPD5 is a potential therapy for patients with DC and reduced TERC levels.
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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.