TCAB1 prevents nucleolar accumulation of the telomerase RNA to promote telomerase assembly

Localization of a wide variety of RNAs to non-membrane bound cellular compartments such as nucleoli, Cajal bodies, and stress-granules is critical for their function and stability. The molecular mechanisms that underly the recruitment and exclusion of specific RNAs from these phase-separated organelles is poorly understood. Telomerase is a ribonucleoprotein (RNP), that is composed of the reverse transcriptase protein TERT, the telomerase RNA (TR), and several auxiliary proteins that associate with TR, including TCAB1. Here we show that, that in the absence of TCAB1, TR is trapped in the nucleolus, while TERT localizes to the nucleoplasm and is excluded from the nucleolus, which prevents telomerase assembly. Thus, nucleolar phase separation constitutes a barrier that counteracts telomerase assembly and TCAB1 is required to exclude the telomerase RNA from the nucleolus. Our work provides general insight into the mechanism and functional consequences of RNA recruitment to non-membrane bound organelles and proposes a new model explaining the critical role of TCAB1 in telomerase function.