Genetics of human telomere biology disorders

de Lange, T. Shelterin-mediated telomere protection. Annu. Rev. Genet. 52, 223–247 (2018).

PubMed  Google Scholar 

Gilson, E. & Geli, V. How telomeres are replicated. Nat. Rev. Mol. Cell Biol. 8, 825–838 (2007).

CAS  PubMed  Google Scholar 

Rossiello, F., Jurk, D., Passos, J. F. & d’Adda di Fagagna, F. Telomere dysfunction in ageing and age-related diseases. Nat. Cell Biol. 24, 135–147 (2022).

CAS  PubMed  PubMed Central  Google Scholar 

Bertuch, A. A. The molecular genetics of the telomere biology disorders. RNA Biol. 13, 696–706 (2016).

PubMed  Google Scholar 

Alder, J. K. & Armanios, M. Telomere-mediated lung disease. Physiol. Rev. 102, 1703–1720 (2022).

PubMed  PubMed Central  Google Scholar 

Demanelis, K. et al. Determinants of telomere length across human tissues. Science 369, eaaz6876 (2020).

PubMed  PubMed Central  Google Scholar 

Blasco, M. A. Mice with bad ends: mouse models for the study of telomeres and telomerase in cancer and aging. EMBO J. 24, 1095–1103 (2005).

CAS  PubMed  PubMed Central  Google Scholar 

Greenberg, R. A., Allsopp, R. C., Chin, L., Morin, G. B. & DePinho, R. A. Expression of mouse telomerase reverse transcriptase during development, differentiation and proliferation. Oncogene 16, 1723–1730 (1998).

CAS  PubMed  Google Scholar 

Kipling, D. & Cooke, H. J. Hypervariable ultra-long telomeres in mice. Nature 347, 400–402 (1990).

CAS  PubMed  Google Scholar 

Heiss, N. S. et al. X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat. Genet. 19, 32–38 (1998).

CAS  PubMed  Google Scholar 

Lai, T. P., Wright, W. E. & Shay, J. W. Comparison of telomere length measurement methods. Philos. Trans. R. Soc. Lond. B Biol. Sci. 373, 20160451 (2018).

PubMed  PubMed Central  Google Scholar 

Alter, B. P. et al. Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. Blood 110, 1439–1447 (2007).

CAS  PubMed  PubMed Central  Google Scholar 

Alder, J. K. et al. Diagnostic utility of telomere length testing in a hospital-based setting. Proc. Natl Acad. Sci. USA 115, E2358–E2365 (2018). By examining telomere length and clinical features of a cohort of 100 patients with TBD, this work demonstrated that the degree of telomere shortening inversely correlated with the age at diagnosis and the TBD phenotype.

PubMed  PubMed Central  Google Scholar 

Roake, C. M. & Artandi, S. E. Regulation of human telomerase in homeostasis and disease. Nat. Rev. Mol. Cell Biol. 21, 384–397 (2020).

CAS  PubMed  PubMed Central  Google Scholar 

Meyerson, M. et al. hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell 90, 785–795 (1997).

CAS  PubMed  Google Scholar 

Bodnar, A. G. et al. Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349–352 (1998). This study demonstrates that ectopic expression of TERT is sufficient to immortalize human somatic cells.

CAS  PubMed  Google Scholar 

Nault, J. C., Ningarhari, M., Rebouissou, S. & Zucman-Rossi, J. The role of telomeres and telomerase in cirrhosis and liver cancer. Nat. Rev. Gastroenterol. Hepatol. 16, 544–558 (2019).

PubMed  Google Scholar 

Lorbeer, F. K. & Hockemeyer, D. TERT promoter mutations and telomeres during tumorigenesis. Curr. Opin. Genet. Dev. 60, 56–62 (2020).

CAS  PubMed  Google Scholar 

Greider, C. W. Telomerase is processive. Mol. Cell. Biol. 11, 4572–4580 (1991).

CAS  PubMed  PubMed Central  Google Scholar 

Armanios, M. Y. et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N. Engl. J. Med. 356, 1317–1326 (2007).

CAS  PubMed  Google Scholar 

Tsakiri, K. D. et al. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc. Natl Acad. Sci. USA 104, 7552–7557 (2007).

CAS  PubMed  PubMed Central  Google Scholar 

Du, H. Y. et al. Complex inheritance pattern of dyskeratosis congenita in two families with 2 different mutations in the telomerase reverse transcriptase gene. Blood 111, 1128–1130 (2008).

CAS  PubMed  PubMed Central  Google Scholar 

Aspesi, A. et al. Compound heterozygosity for two new TERT mutations in a patient with aplastic anemia. Pediatr. Blood Cancer 55, 550–553 (2010).

PubMed  Google Scholar 

Gramatges, M. M., Qi, X., Sasa, G. S., Chen, J. J. & Bertuch, A. A. A homozygous telomerase T-motif variant resulting in markedly reduced repeat addition processivity in siblings with Hoyeraal Hreidarsson syndrome. Blood 121, 3586–3593 (2013).

CAS  PubMed  PubMed Central  Google Scholar 

Niaz, A. et al. Functional interaction between compound heterozygous TERT mutations causes severe telomere biology disorder. Blood Adv. 6, 3779–3791 (2022).

CAS  PubMed  Google Scholar 

Cepni, E., Satkin, N. B., Moheb, L. A., Rocha, M. E. & Kayserili, H. Biallelic TERT variant leads to Hoyeraal-Hreidarsson syndrome with additional dyskeratosis congenita findings. Am. J. Med. Genet. Part A 188, 1226–1232 (2022).

CAS  PubMed  Google Scholar 

Stockklausner, C. et al. A novel autosomal recessive TERT T1129P mutation in a dyskeratosis congenita family leads to cellular senescence and loss of CD34+ hematopoietic stem cells not reversible by mTOR-inhibition. Aging 7, 911–927 (2015).

CAS  PubMed  PubMed Central  Google Scholar 

Marrone, A. et al. Telomerase reverse-transcriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. Blood 110, 4198–4205 (2007).

CAS  PubMed  Google Scholar 

Roake, C. M. et al. Disruption of telomerase RNA maturation kinetics precipitates disease. Mol. Cell 74, 688–700.e683 (2019). This work demonstrates that a feedforward pathway of hTR oligoadenylation by PADP5 and deadenylation by PARN regulates the rate of hTR maturation.

CAS  PubMed  PubMed Central  Google Scholar 

Qin, J. & Autexier, C. Regulation of human telomerase RNA biogenesis and localization. RNA Biol. 18, 305–315 (2021).

CAS  PubMed  Google Scholar 

Tseng, C. K. et al. Human telomerase RNA processing and quality control. Cell Rep. 13, 2232–2243 (2015). This work demonstrates that the nuclear exosome competes with PARN to regulate the maturation of hTR molecule.

CAS  PubMed  Google Scholar 

Nguyen, T. H. D. et al. Cryo-EM structure of substrate-bound human telomerase holoenzyme. Nature 557, 190–195 (2018). Using cryo-electron microscopy, this study reveals a flexible bi-lobed structure of human telomerase holoenzyme bound to its DNA substrate and provides new insights into the impact of disease-associated dyskerin mutations.

CAS  PubMed  PubMed Central  Google Scholar 

Vulliamy, T. et al. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 413, 432–435 (2001).

CAS  PubMed  Google Scholar 

Collopy, L. C. et al. Triallelic and epigenetic-like inheritance in human disorders of telomerase. Blood 126, 176–184 (2015).

CAS  PubMed  PubMed Central  Google Scholar 

Egan, E. D. & Collins, K. Biogenesis of telomerase ribonucleoproteins. RNA 18, 1747–1759 (2012).

CAS  PubMed  PubMed Central  Google Scholar 

Shukla, S., Schmidt, J. C., Goldfarb, K. C., Cech, T. R. & Parker, R. Inhibition of telomerase RNA decay rescues telomerase deficiency caused by dyskerin or PARN defects. Nat. Struct. Mol. Biol. 23, 286–292 (2016).

CAS  PubMed  PubMed Central  Google Scholar 

Knight, S. W. et al. X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene. Am. J. Hum. Genet. 65, 50–58 (1999).

CAS  PubMed  PubMed Central  Google Scholar 

Ghanim, G. E. et al. Structure of human telomerase holoenzyme with bound telomeric DNA. Nature 593, 449–453 (2021).

CAS  PubMed  PubMed Central  Google Scholar 

Alder, J. K. et al. Telomere phenotypes in females with heterozygous mutations in the dyskeratosis congenita 1 (DKC1) gene. Hum. Mutat. 34, 1481–1485 (2013).

CAS  PubMed  PubMed Central  Google Scholar 

Xu, J. et al. Investigation of chromosome X inactivation and clinical phenotypes in female carriers of DKC1 mutations. Am. J. Hematol. 91, 1215–1220 (2016).

CAS  PubMed  PubMed Central  Google Scholar 

Walne, A. J. et al. Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one subtype due to mutations in the telomerase-associated protein NOP10. Hum. Mol. Genet. 16, 1619–1629 (2007).

CAS  PubMed  Google Scholar 

Trahan, C., Martel, C. & Dragon, F. Effects of dyskeratosis congenita mutations in dyskerin, NHP2 and NOP10 on assembly of H/ACA pre-RNPs. Hum. Mol. Genet. 19, 825–836 (2010).

CAS  PubMed  Google Scholar 

Kannengiesser, C. et al. First heterozygous NOP10 mutation in familial pulmonary fibrosis. Eur. Respir. J. 55, 1902465 (2020).

CAS  PubMed  Google Scholar 

Manali, E. D

留言 (0)

沒有登入
gif