Human telomerase RNP biogenesis. The human TER, hTR, is transcribed by RNA polymerase II as a precursor that cotranscriptionally assembles with the H/ACA protein heterotrimer of dyskerin, NHP2, and NOP10 bound to the H/ACA RNP assembly chaperone NAF1. This process is aided by the dyskerin chaperone SHQ1 and a complex of NUFIP and the helicases RUVBL1 and RUVBL2. NUFIP interacts with NHP2, and the RUVBL1/RUVBL2 heterodimer interacts with dyskerin to promote H/ACA RNP assembly. The hTR precursor transcript is then processed at its 3′ end by an unknown mechanism. The G-quadruplex structure that can form near the 5′ end, represented by a wavy line, is resolved by the helicase DHX36. Then, NAF1 is exchanged for the mature H/ACA RNP protein GAR1, and sTGS1 modifies the 5′ cap to TMG, indicated by a diamond. TCAB1 and TERT bind to hTR in the active telomerase holoenzyme.
