TCAB1 prevents nucleolar accumulation of the telomerase RNA to facilitate telomerase assembly
Basma M. Klump,
Gloria I. Perez,
Eric M. Patrick,
Kate Adams-Boone,
Scott B. Cohen,
Li Han,
Kefei Yu,
Jens C. Schmidt
Affiliations
Basma M. Klump
Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI, USA; College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA; Cellular and Molecular Biology Graduate Program, College of Natural Sciences, Michigan State University, East Lansing, MI, USA
Gloria I. Perez
Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI, USA
Eric M. Patrick
Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI, USA
Kate Adams-Boone
Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI, USA
Scott B. Cohen
Children’s Medical Research Institute and University of Sydney, Westmead, NSW 2145, Australia
Li Han
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA
Kefei Yu
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA
Jens C. Schmidt
Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI, USA; Department of Obstetrics, Gynecology, and Reproductive Biology, Michigan State University, East Lansing, MI, USA; Corresponding author
Summary: 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.
