Telomerase RNA TLC1 Shuttling to the Cytoplasm Requires mRNA Export Factors and Is Important for Telomere Maintenance

• The telomerase RNA, TLC1, requires mRNA export factors for nuclear exit
• TLC1 physically interacts with Mex67 and Dbp5
• Nuclear retention of TLC1 leads to defects in telomerase formation
• Retention of TLC1 in the nucleus leads to telomere shortening

SummaryTelomerases 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.

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