A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis.
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.
Venteicher
Andrew S
AS
Department of Medicine, Stanford School of Medicine, Stanford, CA 94305, USA.
Abreu
Eladio B
EB
Meng
Zhaojing
Z
McCann
Kelly E
KE
Terns
Rebecca M
RM
Veenstra
Timothy D
TD
Terns
Michael P
MP
Artandi
Steven E
SE
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D020541:Coiled Bodies / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D019098:Telomerase / Q000737:chemistry / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*
D018797:Cell Cycle Proteins; C112148:DKC1 protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase; C535133:WRAP53 protein, human