Journal
SCIENCE
Volume 323, Issue 5914, Pages 644-648Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1165357
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Funding
- Medical Scientist Training Program [GM07365]
- NCI [CA104676, NO1-CO-12400, CA111691, CA125453]
- Leukemia and Lymphoma Society Specialized Centers of Research [7007-09]
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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.
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