Telomerase is a ribonucleoprotein enzyme that repairs the ends of telomeres that otherwise shorten progressively upon each successive cell division. Telomerase has both a protein (TP1, TEP1) and an RNA component (TERC, TRC3). The RNA component acts as a template for the addition of telomeric repeat sequences. Feng et al. (1995) cloned the 451-nucleotide gene for the telomerase RNA component, which they designated TRC3 (telomerase RNA candidate 3). They showed that antisense TRC3 inhibited telomerase function in vitro, and copurified with telomerase. TRC3 is highly expressed in the germline and in tumor cell lines, in which there is high telomerase activity, and at lower levels in kidney, prostate, and liver, in which there is no detectable telomerase activity. Stem cells and cancer cells can divide indefinitely partly because they express telomerase (Zhu et al., 1996). Telomerase activity was detected in fetal, newborn, and adult testes and ovaries, but not in mature spermatozoa or oocytes (Wright et al.,1996).Lavranos et al. (1999) show that ovarian cells contain telomerase ribonucleic acid component in bovine follicles and propose, that they arise from a population of stem cells.
NCBI Summary:
Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, and an RNA component, encoded by this gene, that serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells resulting in progressive shortening of telomeres. Deregulation of telomerase expression in somatic cells may be involved in oncogenesis. Studies in mouse suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Mutations in this gene cause autosomal dominant dyskeratosis congenita, and may also be associated with some cases of aplastic anemia.
General function
Cell death/survival, Cell cycle regulation
Comment
Cells arrested at the G1/S phase of the cell cycle
showed similar levels of telomerase to asynchronous cultures; progression through the S phase was associated with increased telomerase activity. The highest level of telomerase activity was detected in S-phase cells. In contrast, cells arrested at G2/M phase of the cell cycle were almost devoid of telomerase activity. Diverse cell cycle blockers, including transforming growth factor beta1 and cytotoxic agents, also caused inhibition of telomerase activity (Zhu et al., 1996).
Cellular localization
Nuclear
Comment
Ovarian function
Oogenesis
Comment
Eisenhauer et al. (1997) demonstrated that telomerase activity was found in oocytes from early antral and preovulatory follicles, as well as in ovulated oocytes. The level of enzyme activity in early antral and preovulatory follicles was comparable to that of the immortalized 293 cells, while levels in ovulated oocytes were 50-fold lower.
Expression regulated by
Comment
Ovarian localization
Oocyte, Granulosa, Surface epithelium
Comment
Telomerase activity was found in oocytes from early antral and preovulatory follicles, as well as in ovulated oocytes (Eisenhauer et al., 1997
Follicle stages
Secondary, Antral, Preovulatory
Comment
Telomerase activity was highest in the small preantral follicles, declining at the 1-mm stage and even further at the 3-mm stage. Telomerase mRNA was detected by in situ hybridization in granulosa cells of growing follicles but not primordial follicles (Lavranos et al., 1999
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: Terc -/-
type: null mutation fertility: fertile Comment:Blasco et al. (1997) deleted the telomerase RNA
component from the mouse germline. Terc -/- mice lacked detectable telomerase activity yet were viable for the 6
generations analyzed. Late-generation animals exhibited defective spermatogenesis, with increased programmed cell death (apoptosis) and decreased proliferation in the testis (Lee et al., 1998).