Many Functions of Telomerase Components: Certainties, Doubts, and Inconsistencies
Abstract
:1. Introduction
2. Telomerase: Function and Components
2.1. Telomerase Function
2.2. TERT Structure
2.3. TERC Structure
2.4. Secondary and Accessory Proteins
2.5. Has Telomerase Any Non-Telomeric Function?
2.5.1. Addition of Telomeric Repeats at Double-Strand Break Sites?
2.5.2. NOP2-Dependent Recruitment of Telomerase to Cyclin D1 Promoter
3. TERT Non-Telomeric Functions
3.1. Gene Regulation
3.1.1. NF-κB Pathway
3.1.2. Wnt/β-Catenin Pathway
3.1.3. pRb and Cyclins
3.1.4. Ribosomal DNA
3.1.5. RNA Polymerase III Target Genes
3.1.6. Transcriptomic Studies
3.2. An RNA-Dependent RNA Polymerase?
3.3. TERT and Mitochondria
3.3.1. Shuttling of TERT between Nucleus, Cytoplasm and Mitochondria
3.3.2. TERT Association with mtDNA
3.3.3. Controversial Effects of TERT in Mitochondria
3.4. Cellular Effects
3.5. Alternative Isoforms of TERT and Their Functions
4. TERC Non-Telomeric Functions
4.1. Gene Regulation
4.2. New Actors in the Plot
4.2.1. RPL22
4.2.2. DNA-PK
4.3. TERC and Mitochondria
4.4. TERC-Derived Small RNA
4.5. Translation of TERC?
4.5.1. Prediction of TERC Protein-Coding Ability
4.5.2. Evidence of Absence or Absence of Evidence?
4.5.3. TERP
4.6. Cellular Effects
5. The Network of TERT and TERC Functions and Interactions
6. Open Questions for Future Research
7. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Cell Type | TERT Expression | TERC Silencing | TERC Overexpression | TERC-53 Overexpression |
---|---|---|---|---|
Human Fibroblasts | No | No effects [205,206] | ||
Human Fibroblasts | No | Faster senescence [185] | ||
Human BMSCs | No [210] | Senescence [146] | ||
Human CD4 T cells | Yes [147] | Apoptosis [147] | Reduction of DM-induced apoptosis [147] | |
Human ESCs | Yes [205] | Apoptosis [205] | Reduction of DOX-induced apoptosis [205] | |
HeLa and HCT116 cancer cells | Yes | Apoptosis [142,143] |
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Udroiu, I.; Marinaccio, J.; Sgura, A. Many Functions of Telomerase Components: Certainties, Doubts, and Inconsistencies. Int. J. Mol. Sci. 2022, 23, 15189. https://doi.org/10.3390/ijms232315189
Udroiu I, Marinaccio J, Sgura A. Many Functions of Telomerase Components: Certainties, Doubts, and Inconsistencies. International Journal of Molecular Sciences. 2022; 23(23):15189. https://doi.org/10.3390/ijms232315189
Chicago/Turabian StyleUdroiu, Ion, Jessica Marinaccio, and Antonella Sgura. 2022. "Many Functions of Telomerase Components: Certainties, Doubts, and Inconsistencies" International Journal of Molecular Sciences 23, no. 23: 15189. https://doi.org/10.3390/ijms232315189