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Cell Rep. 2014 Sep 25;8(6):1630-1638. doi: 10.1016/j.celrep.2014.08.021. Epub 2014 Sep 15.

Telomerase RNA TLC1 shuttling to the cytoplasm requires mRNA export factors and is important for telomere maintenance.

Author information

1
Abteilung für Molekulare Genetik, Institut für Mikrobiologie und Genetik, Göttinger Zentrum für Molekulare Biowissenschaften (GZMB), Georg-August Universität Göttingen, 37077 Göttingen, Germany.
2
Abteilung für Molekulare Genetik, Institut für Mikrobiologie und Genetik, Göttinger Zentrum für Molekulare Biowissenschaften (GZMB), Georg-August Universität Göttingen, 37077 Göttingen, Germany. Electronic address: heike.krebber@biologie.uni-goettingen.de.

Abstract

Telomerases protect the ends of linear chromosomes from shortening. They are composed of an RNA (TLC1 in S. cerevisiae) and several proteins. TLC1 undergoes several maturation steps before it is exported into the cytoplasm to recruit the Est proteins for complete assembly. The mature telomerase is subsequently reimported into the nucleus, where it fulfills its function on telomeres. Here, we show that TLC1 export into the cytoplasm requires not only the Ran GTPase-dependent karyopherin Crm1/Xpo1 but also the mRNA export machinery. mRNA export factor mutants accumulate mature and export-competent TLC1 RNAs in their nuclei. Moreover, TLC1 physically interacts with the mRNA transport factors Mex67 and Dbp5/Rat8. Most importantly, we show that the nuclear export of TLC1 is an essential step for the formation of the functional RNA containing enzyme, because blocking TLC1 export in the mex67-5 xpo1-1 double mutant prevents its cytoplasmic maturation and leads to telomere shortening.

PMID:
25220466
DOI:
10.1016/j.celrep.2014.08.021
[Indexed for MEDLINE]
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