TY - JOUR
T1 - A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis
AU - Venteicher, Andrew S.
AU - Abreu, Eladio B.
AU - Meng, Zhaojing
AU - McCann, Kelly E.
AU - Terns, Rebecca M.
AU - Veenstra, Timothy D.
AU - Terns, Michael P.
AU - Artandi, Steven E.
PY - 2009/1/30
Y1 - 2009/1/30
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=59149095154&partnerID=8YFLogxK
U2 - 10.1126/science.1165357
DO - 10.1126/science.1165357
M3 - Article
C2 - 19179534
AN - SCOPUS:59149095154
SN - 0036-8075
VL - 323
SP - 644
EP - 648
JO - Science
JF - Science
IS - 5914
ER -
