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

Localization of a variety of RNAs to non-membrane-bound cellular compartments such as nucleoli and Cajal bodies is critical for their stability and function. The molecular mechanisms that underly the recruitment and exclusion of RNAs from these phase-separated organelles is incompletely understood. Telomerase is a ribonucleoprotein composed of the reverse transcriptase protein telomerase reverse transcriptase (TERT), the telomerase RNA (TR), and several auxiliary proteins, including TCAB1. Here we show that in the absence of TCAB1, a large fraction of TR is tightly bound to the nucleolus, while TERT is largely excluded from the nucleolus, reducing telomerase assembly. This suggests that nuclear compartmentalization by the non-membrane-bound nucleolus counteracts telomerase assembly, and TCAB1 is required to retain TR in the nucleoplasm. Our work provides insight into the mechanism and functional consequences of RNA recruitment to organelles formed by phase separation and demonstrates that TCAB1 plays an important role in telomerase assembly. [Display omitted] •TCAB1 facilitates telomerase assembly in cancer cells•In the absence of TCAB1, the telomerase RNA is sequestered in the nucleolus•TCAB1 is not required for telomerase catalysis•TCAB1 is excluded from nucleoli and prevents entry of the telomerase RNA into the nucleolus Klump et al. show that TCAB1, a telomerase cofactor, facilitates telomerase assembly. The results indicate that TCAB1 is not required for telomerase catalysis and that TCAB1 association with the telomerase RNA prevents its entry into the nucleolus to facilitate its interaction with the telomerase reverse transcriptase.