Nucleolar localization of TERT is unrelated to telomerase function in human cells.
Telomerase maintains telomere length and has been implicated in both aging and carcinogenesis of human cells. This enzyme is a specialized ribonucleoprotein (RNP) complex, minimally consisting of two essential components: the protein catalytic subunit TERT (telomerase reverse transcriptase) and the integral RNA moiety TR (telomerase RNA, TERC). Both TERT and TR have been found to localize to nucleoli within the nucleus, leading to the suggestion of nucleoli as the site for telomerase RNP biogenesis in human cells. However, whether this statement is true or not has not yet been convincingly demonstrated. Here, we identify that residues 965-981 of the human TERT polypeptide constitute an active nucleolar-targeting signal (NTS) essential for mediating human TERT nucleolar localization. Mutational inactivation of this NTS completely disrupted TERT nucleolar translocation in both normal and malignant human cells. Most interestingly, such a TERT mutant still retained the capacity to activate telomerase activity, maintain telomere length and extend the life-span of cellular proliferation, as does wild-type TERT, in BJ cells (normal fibroblasts). Therefore, our data suggest that TERT nucleolar localization is unrelated to telomerase function in human cells.
Lin
Jian
J
Laboratory of Tumor and Molecular Biology, Beijing Institute of Biotechnology, 27 Taiping Road, Beijing, People's Republic of China.
Jin
Rui
R
Zhang
Bin
B
Chen
Hao
H
Bai
Yun Xiu
YX
Yang
Ping Xun
PX
Han
Su Wen
SW
Xie
Yao Hua
YH
Huang
Pei Tang
PT
Huang
Cuifen
C
Huang
Jun Jian
JJ
D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism; D006801:Humans; D051379:Mice; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism
D019913:Nuclear Localization Signals; D012261:Ribonucleoproteins; C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase