Published on Thu May 27 2021

TCAB1 is necessary for telomerase assembly

Al-Masraf, B. S., Perez, G. I., Adams-Boone, K., Cohen, S. B., Han, L., Yu, K., Schmidt, J. C.

The ribonucleoprotein telomerase counteracts telomere shortening by adding repetitive sequences to the ends of human chromosomes. Telomerase is composed of the reverse transcriptase TERT, the telomer enzyme RNA, and several auxiliary proteins. TCAB1 is necessary for telome

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Abstract

The ribonucleoprotein telomerase counteracts telomere shortening by adding repetitive sequences to the ends of human chromosomes. Telomerase is composed of the reverse transcriptase TERT, the telomerase RNA, and several auxiliary proteins that associate with the telomerase RNA, including TCAB1. TCAB1 is necessary for telomere maintenance in human cells and has been proposed to play a role in telomerase trafficking to Cajal bodies and telomeres, and in telomerase RNA folding. Here we show that, contrary to previous findings, TCAB1 is essential for telomerase assembly. We demonstrate that in the absence of TCAB1, the telomerase RNA is trapped in the nucleolus, a phase separated nuclear organelle, while TERT localizes to the nucleoplasm and is excluded from the nucleolus. Thus, nucleolar phase separation constitutes a barrier that counteracts telomerase assembly and TCAB1 is required to extract the telomerase RNA from the nucleolus, providing a molecular mechanism for the essential role of TCAB1 in telomerase function.