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 telomerase ribonucleoprotein catalyzes the addition of new telomeres on the chromosome ends. The ribonucleoprotein complex responsible for telomerase activity had been purified in ciliates. Purified tetrahymena telomerase contains an RNA and 2 protein components, p80 and p95. The p80 component can be specifically cross linked to telomerase RNA, whereas the p95 component binds and cross links to single-stranded, telomeric DNA. Harrington et al. (1997) identified a cDNA encoding a tetrahymena p80 homolog from a murine colonic crypt expressed sequence tag (EST) database. 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 and propose, that they arise from a population of stem cells.
NCBI Summary:
This gene product is a component of the ribonucleoprotein complex responsible for telomerase activity which catalyzes the addition of new telomeres on the chromosome ends. The telomerase-associated proteins are conserved from ciliates to humans. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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, Early embryo development
Comment
TA is more significant for predicting the outcome of IVF than TL in granulosa cells. Wang W 2014 et al.
Our previous study demonstrated that granulosa cells(GCs) have the potential to proliferate and that the telomerase activity(TA) of GCs may predict the clinical outcomes of in vitro fertilisation(IVF). However, there have always been different opinions regarding the significance of TA and telomere length(TL). Thus, the current study compared the effects of these two parameters on the outcome of IVF in the same individuals. TL did not differ significantly between the pregnancy group and the non-pregnancy group. The TA, number of retrieved oocytes and rate of blastocyst transfer were significantly higher in the pregnancy group (0.8825 OD ?mm, 12.75 ? 2.20 and 34.48%, respectively, in the pregnancy group vs. 0.513 OD ?mm, 11.60 ? 0.93 and 14.89%, respectively, in the non-pregnancy group (P < 0.05)), while basal FSH levels were lower in the pregnancy group than in the non-pregnancy group. The subjects did not differ in ovarian stimulation or other clinical characteristics. A TA increase of 1 OD?m increased the chance of becoming pregnant 4.769-fold (OR:5.769, 95% CI:1.434-23.212, P < 0.014). The areas under the receiver operating characteristic(ROC) curves were 0.576 for TL and 0.674 for TA(P = 0.271 and P < 0. 012, respectively). The corresponding cut-off points were 4.470 for TL and 0.650 OD?m for TA. These results demonstrated that TA is a better predictor than TL of pregnancy outcome following IVF. No other clinical parameters, including age, baseline FSH level or peak estradiol level, distinguished between the pregnant and non-pregnant groups as effectively as TA.
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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).
In situ hybridization showed two different patterns of staining in the membrana granulosa of antral follicles: staining in the middle and antral layers, and staining in the middle and basal layers. No staining was detected in oocytes (Lavranos et al., 1999).
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
POF (premature ovarian failure)
Mutations
1 mutations
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: Impaired telomere length and telomerase activity in peripheral blood leukocytes and granulosa cells in patients with biochemical primary ovarian insufficiency. Xu X et al. (2016) Are telomere length and telomerase activity associated with biochemical primary ovarian insufficiency (POI)? Shortened telomere length and diminished telomerase activity were associated with biochemical POI. POI is a result of pathological reproductive aging and encompasses occult, biochemical and overt stages. Studies have indicated telomere length as a biomarker for biological aging. A total of 120 patients with biochemical POI and 279 control women were recruited by the Center for Reproductive Medicine of Shandong University. Telomere length in peripheral blood leukocytes (LTL) and granulosa cells (GTL) was measured using a modified Quantitative Polymerase Chain Reaction technique. The relative telomerase activity (RTA) in granulosa cells was detected using a modified quantitative-telomeric repeat amplification protocol assay. After adjusting for age, patients with biochemical POI (n = 120) exhibited significantly shorter LTLs (0.75 ± 0.09 vs 1.79 ± 0.12, P < 0.001; OR = 0.54, 95% CI = 0.43-0.68) and GTLs (0.78 ± 0.09 vs 1.90 ± 0.23, P < 0.001; OR = 0.54, 95% CI = 0.41-0.70) than the controls (n = 279 for LTLs; n = 90 for GTLs). Significantly diminished RTAs in granulosa cells were detected in patients with biochemical POI (n = 31) compared with the controls (n = 38) (1.57 ± 0.59 vs 4.63 ± 0.93, P = 0.025; OR = 0.84, 95% CI = 0.72-0.98). N/A. The cross-sectional nature of this study might have its limit in telomere length as well as telomerase activity along with the progressing decline in ovarian function. These findings suggest that telomere length and telomerase activity may be considered as indicators for progression of ovarian decline. This research was supported by the National Basic Research Program of China (973 Program) (2012CB944700), Science research foundation item of no-earnings health vocation (201402004) and the National Natural Science Foundation of China (31471352, 81270662, 81471509, 81300461, 81522018). The authors have no potential conflict of interest to declare.//////////////////