Telomerase-associated protein TEP1 is not essential for telomerase activity or telomere length maintenance in vivo.
TEP1 is a mammalian telomerase-associated protein with similarity to the Tetrahymena telomerase protein p80. Like p80, TEP1 is associated with telomerase activity and the telomerase reverse transcriptase, and it specifically interacts with the telomerase RNA. To determine the role of mTep1 in telomerase function in vivo, we generated mouse embryonic stem (ES) cells and mice lacking mTep1. The mTep1-deficient (mTep1(-/-)) mice were viable and were bred for seven successive generations with no obvious phenotypic abnormalities. All murine tissues from mTep1(-/-) mice possessed a level of telomerase activity comparable to that in wild-type mice. In addition, analysis of several tissues that normally lack telomerase activity revealed no reactivation of telomerase activity in mTep1(-/-) mice. Telomere length, even in later generations of mTep1(-/-) mice, was equivalent to that in wild-type animals. ES cells deficient in mTep1 also showed no detectable alteration in telomerase activity or telomere length with increased passage in culture. Thus, mTep1 appears to be completely dispensable for telomerase function in vivo. Recently, TEP1 has been identified within a second ribonucleoprotein (RNP) complex, the vault particle. TEP1 can also specifically bind to a small RNA, vRNA, which is associated with the vault particle and is unrelated in sequence to mammalian telomerase RNA. These results reveal that TEP1 is an RNA binding protein that is not restricted to the telomerase complex and that TEP1 plays a redundant role in the assembly or localization of the telomerase RNP in vivo.
Liu
Y
Y
Ontario Cancer Institute/Amgen Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada.
Snow
B E
BE
Hande
M P
MP
Baerlocher
G
G
Kickhoefer
V A
VA
Yeung
D
D
Wakeham
A
A
Itie
A
A
Siderovski
D P
DP
Lansdorp
P M
PM
Robinson
M O
MO
Harrington
L
L
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002384:Catalysis; D004622:Embryo, Mammalian / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D011233:Precipitin Tests; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins; D011995:Recombination, Genetic; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000378:metabolism; D019098:Telomerase; D016615:Telomere / Q000502:physiology* / Q000648:ultrastructure; D013950:Thymus Gland / Q000166:cytology
D002352:Carrier Proteins; D016601:RNA-Binding Proteins; C498415:Tep1 protein, mouse; D012313:RNA; D019098:Telomerase; C498417:telomerase p80 protein, Tetrahymena