Pharmaceutical Sciences Faculty Publications

A Human Telomerase Holoenzyme Protein Required for Cajal Body Localization and Telomere Synthesis

Document Type

Article

Publication Date

1-30-2009

Journal Title

Science

ISSN

1095-9203

Volume

323

Issue

5914

First Page

644

Last Page

648

DOI

10.1126/science.1165357

PubMed ID

19179534

PubMed Central® ID

PMC2728071

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.

Keywords

Amino acid sequence, cell cycle proteins, cell line, tumor, coiled bodies, immunoprecipitation, molecular chaperones, molecular sequence data, nuclear proteins, RNA, RNA interference, telomerase, telomere

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