S. cerevisiae telomerase RNP biogenesis. S. cerevisiae TLC1 is transcribed by RNA polymerase II, and transcription is terminated by the Nrd1–Nab3–Sen1 pathway. The 3′ end is processed by the nuclear exosome and TRAMP complex, leaving a short adenosine-rich tail that is ultimately removed. Sm protein binding near the 3′ end stabilizes the RNA and recruits the cap hypermethylase Tgs1, which modifies the 5′ cap to TMG, indicated by a diamond. The TERT subunit Est2 binds directly to TLC1. The Ku heterodimer recognizes a distinct binding site on TLC1 to promote RNP accumulation and nuclear import. The regulatory subunit Est1 can bind directly to TLC1 and with Est3 stimulates telomerase function at telomeres.
