RNase P/MRP subunits chaperone telomerase holoenzyme assembly in fission yeast.

Telomerase biogenesis is a multistep process requiring the coordinated action of several accessory factors. In the fission yeast Schizosaccharomyces pombe, the telomerase RNA TER1 undergoes spliceosome-mediated 3'-end processing, followed by association with the Pof8/Bmc1/Thc1 complex, which facilitates binding of the Lsm2-8 complex. Lsm2-8 protects TER1 from nucleolytic degradation and promotes recruitment of the catalytic subunit Trt1. Here, we identify Pop6, Pop7, and Pop100, three subunits of the RNase P/MRP complex, as components of the active telomerase holoenzyme. These proteins associate with a stem-loop-stem structure near the TER1 pseudoknot that resembles the P3 domain found in RNase P/MRP RNAs. A single-nucleotide change within this P3-like loop disrupts Pop protein binding, resulting in reduced telomerase activity and severe telomere shortening. This mutation also impairs the assembly of key telomerase subunits and alters the folding of the template-pseudoknot region of TER1. Our findings reveal a critical role for Pop6, Pop7, and Pop100 in chaperoning TER1 into a conformation that promotes functional telomerase assembly and underscore the remarkable evolutionary plasticity of telomerase biogenesis.