Maturation and shuttling of the yeast telomerase RNP: assembling something new using recycled parts

Abstract

As the limiting component of the budding yeast telomerase, the Tlc1 RNA must undergo multiple consecutive modifications and rigorous quality checks throughout its lifecycle. These steps will ensure that only correctly processed and matured molecules are assembled into telomerase complexes that subsequently act at telomeres. The complex pathway of Tlc1 RNA maturation, involving 5'- and 3'-end processing, stabilisation and assembly with the protein subunits, requires at least one nucleo-cytoplasmic passage. Furthermore, it appears that the pathway is tightly coordinated with the association of various and changing proteins, including the export factor Xpo1, the Mex67/Mtr2 complex, the Kap122 importin, the Sm7 ring and possibly the CBC and TREX-1 complexes. Although many of these maturation processes also affect other RNA species, the Tlc1 RNA exploits them in a new combination and, therefore, ultimately follows its own and unique pathway. In this review, we highlight recent new insights in maturation and subcellular shuttling of the budding yeast telomerase RNA and discuss how these events may be fine-tuned by the biochemical characteristics of the varying processing and transport factors as well as the final telomerase components. Finally, we indicate outstanding questions that we feel are important to be addressed for a complete understanding of the telomerase RNA lifecycle and that could have implications for the human telomerase as well.

Methods that shaped telomerase research

“…Surrounding the catalytic core are a number of proteins that assemble with the RNA scaffold, or between telomerase subunits, some of which are necessary for subcellular localisation and association at telomeres. For yeast, these include Est1, Est3, Pop1 Pop6, Pop7, the yKu70/80 dimer and 3’ Sm7 ring (for a review see Bartle et al 2022 ). For human telomerase they comprise TCAB1, NHP2, GAR1, NOP10 and dyskerin (Nguyen et al 2018 ).…”