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Abstract
Telomeres are special DNA-protein structures that are located at the ends of linear eukaryotic chromosomes. The telomere length determines the proliferation potential of cells. Telomerase is a key component of the telomere length maintenance system. While telomerase is inactive in the majority of somatic cells, its activity determines the clonogenic potential of stem cells as a resource for tissue and organism regeneration. Reactivation of telomerase occurs during the process of immortalization in the majority of cancer cells. Telomerase is a ribonucleoprotein that contains telomerase reverse transcriptase and telomerase RNA components. The RNA processing mechanism of telomerase involves exosome trimming or degradation of the primary precursor. Recent data provide evidence that the competition between the processing and decay of telomerase RNA may regulate the amount of RNA at the physiological level. We show that termination of human telomerase RNA transcription is dependent on its promoter, which engages with the multisubunit complex Integrator to interact with RNA polymerase II and terminate transcription of the human telomerase RNA gene followed by further processing.
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1 Skolkovo Institute of Science and Technology, Center of Life Sciences, Skolkovo, Russia (GRID:grid.454320.4) (ISNI:0000 0004 0555 3608); Lomonosov Moscow State University, Department of Chemistry, Faculty of Bioengineering and Bioinformatics and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow, Russia (GRID:grid.14476.30) (ISNI:0000 0001 2342 9668)
2 Lomonosov Moscow State University, Department of Chemistry, Faculty of Bioengineering and Bioinformatics and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow, Russia (GRID:grid.14476.30) (ISNI:0000 0001 2342 9668)
3 Research Center of Biotechnology of the Russian Academy of Sciences, Institute of Bioengineering, Moscow, Russia (GRID:grid.4886.2) (ISNI:0000 0001 2192 9124)
4 Skolkovo Institute of Science and Technology, Center of Life Sciences, Skolkovo, Russia (GRID:grid.454320.4) (ISNI:0000 0004 0555 3608); Lomonosov Moscow State University, Department of Chemistry, Faculty of Bioengineering and Bioinformatics and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow, Russia (GRID:grid.14476.30) (ISNI:0000 0001 2342 9668); Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia (GRID:grid.418853.3) (ISNI:0000 0004 0440 1573)