ReviewLife and Death of Yeast Telomerase RNA

- Yeast telomerase is composed of a single RNA bound by Est1-3 and Pop1, 6, and 7 proteins.
- The ribonucleoprotein diffuses freely in the nucleus, forming rare stable interactions with telomeres.
- Yeast telomeric repeat-containing RNA clusters telomerase molecules and directs them to short telomeres.
- Cajal bodies are not essential for telomerase function or its delivery to telomeres.

Telomerase reverse transcriptase elongates telomeres to overcome their natural attrition and allow unlimited cellular proliferation, a characteristic shared by stem cells and the majority of malignant cancerous cells. The telomerase holoenzyme comprises a core RNA molecule, a catalytic protein subunit, and other accessory proteins. Malfunction of certain telomerase components can cause serious genetic disorders including dyskeratosis congenita and aplastic anaemia. A hierarchy of tightly regulated steps constitutes the process of telomerase biogenesis, which, if interrupted or misregulated, can impede the production of a functional enzyme and severely affect telomere maintenance. Here, we take a closer look at the budding yeast telomerase RNA component, TLC1, in its long lifetime journey around the cell. We review the extensive knowledge on TLC1 transcription and processing. We focus on exciting recent studies on telomerase assembly, trafficking, and nuclear dynamics, which for the first time unveil striking similarities between the yeast and human telomerase ribonucleoproteins. Finally, we identify questions yet to be answered and new directions to be followed, which, in the future, might improve our knowledge of telomerase biology and trigger the development of new therapies against cancer and other telomerase-related diseases.

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