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First published online June 18, 2008

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The unsolved case of nucleolar TERT

The ribonucleoprotein telomerase extends the replicative lifespan of cells by inhibiting telomere shortening, but little is known about the site of its biogenesis. The two essential components of telomerase both associate with nucleoli in human cells – the RNA moiety (TERC) is processed and matured there, and the protein catalytic subunit (TERT) shuttles between nucleoli and the nucleoplasm. Are nucleoli, therefore, the sites of telomerase biogenesis? On page 2169, Jun Jian Huang and colleagues show that this is unlikely to be so. By analysing a series of TERT-GFP constructs, the authors show that a short, positively charged peptide sequence within the C-terminus of TERT acts as a nucleolar-targeting sequence (NTS). The authors replace three of the positively charged amino acids within the NTS with alanine residues, and show that the mutant protein does not localise to the nucleolus, even in response to DNA damage (which promotes the nucleolar accumulation of TERT in cancer cells). Surprisingly, however, mutant TERT counteracts telomere shortening in both fibroblasts and cancer cells; moreover, the mutant protein extends the replicative lifespan of fibroblasts, as wild-type TERT does. The authors conclude that the nucleolar localisation of TERT is not required for telomerase activity or biogenesis.

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Nucleolar localization of TERT is unrelated to telomerase function in human cells

Jian Lin, Rui Jin, Bin Zhang, Hao Chen, Yun Xiu Bai, Ping Xun Yang, Su Wen Han, Yao Hua Xie, Pei Tang Huang, Cuifen Huang, and Jun Jian Huang
JCS 2008 121: 2169-2176. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?