Expression and Suppression of Human Telomerase RNA

Abstract

Telomeres are maintained by the ribonucleoprotein (RNP) enzyme telomerase, which replenishes telomeres through its unique mechanism of internal RNA-templated addition of telomeric DNA. Telomerase is active in most human cancers, typically because its core protein subunit, TERT, is up-regulated. Although the major known function of telomerase in cancer is to replenish telomeric DNA and maintain cell immortality, the regulation of the RNA component of telomerase is not well understood. In the course of investigations that have implicated telomerase RNA in key aspects of cancer progression, including metastasis, we explored some of the cis-acting elements affecting telomerase RNA expression and knockdown. The expression efficiency and subsequent RNA processing to produce the mature hTER differed considerably among various promoters. Together with other results, these findings establish that the crucial elements of the hTER gene affecting RNA-processing efficiency to produce the mature hTER RNA are the promoter and internal telomerase RNA-coding sequences.