{"doi":"10.1126/science.1165357","title":"A Human Telomerase Holoenzyme Protein Required for Cajal Body Localization and Telomere Synthesis","abstract":"<jats:p>Telomerase is a ribonucleoprotein (RNP) complex that synthesizes telomere repeats in tissue progenitor cells and cancer cells. Active human telomerase consists of at least three principal subunits, including the telomerase reverse transcriptase, the telomerase RNA (TERC), and dyskerin. Here, we identify a holoenzyme subunit, TCAB1 (telomerase Cajal body protein 1), that is notably enriched in Cajal bodies, nuclear sites of RNP processing that are important for telomerase function. TCAB1 associates with active telomerase enzyme, established telomerase components, and small Cajal body RNAs that are involved in modifying splicing RNAs. Depletion of TCAB1 by using RNA interference prevents TERC from associating with Cajal bodies, disrupts telomerase-telomere association, and abrogates telomere synthesis by telomerase. Thus, TCAB1 controls telomerase trafficking and is required for telomere synthesis in human cancer cells.</jats:p>","journal":"Science","year":2009,"id":34536,"datarank":10.15758086866452,"base_score":6.269096283706261,"endowment":6.269096283706261,"self_citation_contribution":0.9403644425559393,"citation_network_contribution":9.21721642610858,"self_endowment_contribution":0.9403644425559393,"citer_contribution":9.21721642610858,"corpus_percentile":null,"corpus_rank":null,"citation_count":527,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":14,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":178726,"name":"Eladio B. Abreu","orcid":null,"position":1,"is_corresponding":false},{"id":178728,"name":"Zhaojing Meng","orcid":null,"position":2,"is_corresponding":false},{"id":178730,"name":"Kelly E. McCann","orcid":null,"position":3,"is_corresponding":false},{"id":174354,"name":"Rebecca M. Terns","orcid":null,"position":4,"is_corresponding":false},{"id":63762,"name":"Timothy D. Veenstra","orcid":"0000-0003-2941-0225","position":5,"is_corresponding":false},{"id":174355,"name":"Michael P. Terns","orcid":null,"position":6,"is_corresponding":false},{"id":74110,"name":"Steven E. Artandi","orcid":"0000-0001-5580-7512","position":7,"is_corresponding":false},{"id":11411,"name":"Andrew S. Venteicher","orcid":"0000-0003-0643-0493","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":6.269096283706261,"endowment":6.269096283706261,"datacite_reuse_total":14,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19179534","pmcid":"PMC2728071","openalex_id":"https://openalex.org/W2014414194","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM07365","title":null},{"funder_name":"NCI NIH HHS","grant_id":"N01 CO012400","title":null},{"funder_name":"NCI NIH HHS","grant_id":"N01-CO-12400","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA111691","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA125453","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM007365","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA125453","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA111691","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA104676","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA104676","title":null}],"total_grants":10,"fwci":23.2028,"citation_percentile":0.99774345,"influential_citations":48,"citation_trend":[{"year":2012,"count":35},{"year":2013,"count":35},{"year":2014,"count":40},{"year":2015,"count":37},{"year":2016,"count":43},{"year":2017,"count":29},{"year":2018,"count":30},{"year":2019,"count":26},{"year":2020,"count":32},{"year":2021,"count":31},{"year":2022,"count":22},{"year":2023,"count":20},{"year":2024,"count":28},{"year":2025,"count":17},{"year":2026,"count":7}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2728071","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc2728071?pdf=render","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2728071","host_type":"repository"},{"url":"https://www.science.org/doi/pdf/10.1126/science.1165357","host_type":"publisher"},{"url":"https://doi.org/10.1126/science.1165357","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19179534","host_type":"repository"},{"url":"https://www.jstor.org/stable/20402976?seq=1#metadata_info_tab_contents","host_type":"repository"}],"fields_of_study":["Telomeres, Telomerase, and Senescence","RNA Interference and Gene Delivery","CRISPR and Genetic Engineering","Medicine","Biology"],"mesh_terms":["Amino Acid Sequence","HeLa Cells","Humans","Molecular Sequence Data","Nuclear Proteins","RNA","Telomere","Cell Cycle Proteins","Molecular Chaperones","Telomerase","Coiled Bodies","RNA Interference","Cell Line, Tumor","Immunoprecipitation","Hela Cells"],"keywords":["Telomerase","Cajal body","Telomere","Telomerase RNA component","Ribonucleoprotein","Telomerase reverse transcriptase","Biology","Cell biology","RNA","Molecular biology","RNA splicing","Genetics","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.26687912.v1","title":"Additional file 5 of Silencing PinX1 enhances radiosensitivity and antitumor-immunity of radiotherapy in non-small cell lung cancer","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26687912","title":"Additional file 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