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PMID: 19179534 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis.

Science (New York, N.Y.) ·Vol. 323 ·No. 5914 ·2009-01-30 ·Pages 644-8

Venteicher AS, Abreu EB, Meng Z, McCann KE, Terns RM, Veenstra TD, Terns MP, Artandi SE

Abstract

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.

MeSH Terms
Amino Acid Sequence Cell Cycle Proteins/metabolism Cell Line, Tumor Coiled Bodies/metabolism HeLa Cells Humans Immunoprecipitation Molecular Chaperones Molecular Sequence Data Nuclear Proteins/metabolism RNA/metabolism RNA Interference Telomerase/chemistry,metabolism Telomere/metabolism
Chemicals
Cell Cycle Proteins DKC1 protein, human Molecular Chaperones Nuclear Proteins telomerase RNA RNA TERT protein, human Telomerase WRAP53 protein, human
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Venteicher Andrew S
Department of Medicine, Stanford School of Medicine, Stanford, CA 94305, USA.
Abreu Eladio B
Meng Zhaojing
McCann Kelly E
Terns Rebecca M
Veenstra Timothy D
Terns Michael P
Artandi Steven E
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1165357
Published
2009-01-30
Pages
644-8
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2728071
Subset
IM
Grants
NIGMS NIH HHS · T32 GM007365 · United States
NCI NIH HHS · R01 CA111691-04 · United States
NCI NIH HHS · R01 CA125453-03 · United States
NCI NIH HHS · R01 CA104676 · United States
NCI NIH HHS · R01 CA111691 · United States
NIGMS NIH HHS · GM07365 · United States
NCI NIH HHS · CA104676 · United States
NCI NIH HHS · R01 CA125453 · United States
NCI NIH HHS · N01CO12400 · United States
NCI NIH HHS · N01-CO-12400 · United States
NCI NIH HHS · CA125453 · United States
NCI NIH HHS · CA111691 · United States
External Links
PubMed source DOI: 10.1126/science.1165357 PMC Full Text View journal details
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