Human telomerase activation requires two independent interactions between telomerase RNA and telomerase reverse transcriptase

Citation
Jr. Mitchell et K. Collins, Human telomerase activation requires two independent interactions between telomerase RNA and telomerase reverse transcriptase, MOL CELL, 6(2), 2000, pp. 361-371
Citations number
31
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR CELL
ISSN journal
10972765 → ACNP
Volume
6
Issue
2
Year of publication
2000
Pages
361 - 371
Database
ISI
SICI code
1097-2765(200008)6:2<361:HTARTI>2.0.ZU;2-Y
Abstract
Inhibition or activation of the reverse transcriptase telomerase can profou ndly affect the proliferative capacity of normal cells and cancers. Here, w e elucidate structural requirements for function of the essential RNA compo nent of human telomerase, hTR. Two motifs within the independently stable H /ACA domain of hTR are required for accumulation of the mature RNA in vivo. However, these motifs can be substituted by a heterologous H/ACA family RN A. Two additional hTR elements are required both in vivo and in vitro for t elomerase catalytic activity. Surprisingly, each of these elements independ ently binds to the telomerase reverse transcriptase. Our results establish fundamental differences between vertebrate and ciliate telomerase ribonucle oprotein architectures and also suggest strategies for the pharmaceutical d evelopment of telomerase-based anticancer therapies.