Telomerase RNA component
(Redirected from
Telomerase RNA
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Ensembl
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| RefSeq (protein) |
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| Location (UCSC) | Chr 3: 169.76 – 169.77 Mb | n/a | |||||||
| PubMed search | [2] | n/a | |||||||
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| Vertebrate telomerase RNA | |
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| Identifiers | |
| Symbol | Telomerase-vert |
| Rfam | RF00024 |
| Other data | |
| RNA type | Gene |
| Domain(s) | Eukaryote; Virus |
| PDB structures | PDBe |
| Ciliate telomerase RNA | |
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| Identifiers | |
| Symbol | Telomerase-cil |
| Rfam | RF00025 |
| Other data | |
| RNA type | Gene |
| Domain(s) | Eukaryote |
| PDB structures | PDBe |
| Saccharomyces cerevisiae telomerase RNA | |
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| Identifiers | |
| Symbol | Sacc_telomerase |
| Rfam | RF01050 |
| Other data | |
| RNA type | Gene |
| Domain(s) | Eukaryote |
| PDB structures | PDBe |
Telomerase RNA component, also known as TR, TER or TERC, is an
Structure
TERC is a
RNP complex.[10] The conserved CR7 domain is also localized at the 3’ end of TERC, and contains a 3nt CAB (Cajal body Localisation) box which binds TCAB1.[10]
Function
Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. This repeat does vary across
oncogenesis. Studies in mice suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks.[12] Homologs of TERC can also be found in the Gallid herpes viruses.[13]
The core domain of TERC contains the
NHP2), which stabilises TERC, increasing telomerase complex formation and overall catalytic activity.[10] The CR7 domain binds TCAB1, which localizes telomerase to cajal bodies, further increasing telomerase catalytic activity.[10] TERC is ubiquitously expressed, even in cells lacking telomerase activity and TERT expression.[15] As a result, various TERT-independent functional roles of TERC have been proposed. 14 genes containing a TERC binding motif are directly transcriptionally regulated by TERC through RNA-DNA triplex formation-mediated increase of expression. TERC-mediated upregulation of Lin37, Trpg1l, tyrobp, Usp16 stimulates the NF-κB pathway, resulting in increased expression and secretion of inflammatory cytokines.[16]
Biosynthesis
Unlike most
PARN, and subsequent 3’-5’ exoribonucleolytic degradation.[8] Extended hTR transcripts are also degraded by the RNA exosome.[8]
The 5’ ends of hTR transcripts are also additionally processed.
5'-methylguanosine cap to an N2,2,7 trimethylguanosine (TMG) cap, which inhibits hTR maturation.[18] Binding of the Dyskerin complex to transcribed H/ACA domains of hTR during transcription promotes termination of transcription.[8]
Control of the relative rates of these various competing pathways that activate or inhibit hTR maturation is a crucial element of regulation of overall telomerase activity.
Clinical Significance
Loss of function
gastric carcinoma.[23] Overexpression of TERC is also observed in inflammatory conditions such as Type II diabetes and multiple sclerosis, due to TERC-mediated activation of the NF-κB inflammatory pathway.[16]
TERC has been implicated as protective in
lung squamous cell carcinoma (LUSC).[25]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000277925 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 9440710.
- PMID 16319170.
- PMID 7739888.
- PMID 7958872.
- PMID 16713250.
- ^ PMID 30930056.
- PMID 31157162.
- ^ PMID 21844345.
- ^ PMID 27245259.
- ^ "Entrez Gene: TERC telomerase RNA component".
- S2CID 24301693.
- PMID 31451513.
- S2CID 61156603.
- ^ PMID 31294790.
- ^ "OMIM Entry - * 602322 - TELOMERASE RNA COMPONENT; TERC". www.omim.org. Retrieved 2020-03-02.
- PMID 32023455.
- OCLC 1023865227.)
{{cite book}}: CS1 maint: location missing publisher (link - OCLC 1053744041.)
{{cite book}}: CS1 maint: location missing publisher (link - PMID 31685833.
- S2CID 53085869.
- S2CID 21966828.
- S2CID 211024218.
- S2CID 209385638.
Further reading
- de Lange T, Jacks T (August 1999). "For better or worse? Telomerase inhibition and cancer". Cell. 98 (3): 273–5. S2CID 14642341.
- Marrone A, Dokal I (December 2004). "Dyskeratosis congenita: molecular insights into telomerase function, ageing and cancer". Expert Reviews in Molecular Medicine. 6 (26): 1–23. S2CID 38163343.
- Yamaguchi H (June 2007). "Mutations of telomerase complex genes linked to bone marrow failures". Journal of Nippon Medical School. 74 (3): 202–9. PMID 17625368.
- Zaug AJ, Linger J, Cech TR (February 1996). "Method for determining RNA 3' ends and application to human telomerase RNA". Nucleic Acids Research. 24 (3): 532–3. PMID 8602368.
- Soder AI, Hoare SF, Muire S, Balmain A, Parkinson EK, Keith WN (April 1997). "Mapping of the gene for the mouse telomerase RNA component, Terc, to chromosome 3 by fluorescence in situ hybridization and mouse chromosome painting". Genomics. 41 (2): 293–4. PMID 9143511.
- Zhao JQ, Hoare SF, McFarlane R, Muir S, Parkinson EK, Black DM, Keith WN (March 1998). "Cloning and characterization of human and mouse telomerase RNA gene promoter sequences". Oncogene. 16 (10): 1345–50. S2CID 2699389.
- Mitchell JR, Wood E, Collins K (December 1999). "A telomerase component is defective in the human disease dyskeratosis congenita". Nature. 402 (6761): 551–5. S2CID 4430482.
- Chen JL, Blasco MA, Greider CW (March 2000). "Secondary structure of vertebrate telomerase RNA". Cell. 100 (5): 503–14. S2CID 15642776.
- Wong KK, Chang S, Weiler SR, Ganesan S, Chaudhuri J, Zhu C, et al. (September 2000). "Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation". Nature Genetics. 26 (1): 85–8. S2CID 1873111.
- Mitchell JR, Collins K (August 2000). "Human telomerase activation requires two independent interactions between telomerase RNA and telomerase reverse transcriptase". Molecular Cell. 6 (2): 361–71. PMID 10983983.
- Imoto I, Pimkhaokham A, Fukuda Y, Yang ZQ, Shimada Y, Nomura N, et al. (August 2001). "SNO is a probable target for gene amplification at 3q26 in squamous-cell carcinomas of the esophagus". Biochemical and Biophysical Research Communications. 286 (3): 559–65. PMID 11511096.
- Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I (September 2001). "The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita". Nature. 413 (6854): 432–5. S2CID 4348062.
- Pruzan R, Pongracz K, Gietzen K, Wallweber G, Gryaznov S (January 2002). "Allosteric inhibitors of telomerase: oligonucleotide N3'-->P5' phosphoramidates". Nucleic Acids Research. 30 (2): 559–68. PMID 11788719.
- Zhang RG, Zhang RP, Wang XW, Xie H (March 2002). "Effects of cisplatin on telomerase activity and telomere length in BEL-7404 human hepatoma cells". Cell Research. 12 (1): 55–62. S2CID 36839452.
- Yang Y, Chen Y, Zhang C, Huang H, Weissman SM (July 2002). "Nucleolar localization of hTERT protein is associated with telomerase function". Experimental Cell Research. 277 (2): 201–9. PMID 12083802.
- Chang JT, Chen YL, Yang HT, Chen CY, Cheng AJ (July 2002). "Differential regulation of telomerase activity by six telomerase subunits". European Journal of Biochemistry. 269 (14): 3442–50. PMID 12135483.
- Gavory G, Farrow M, Balasubramanian S (October 2002). "Minimum length requirement of the alignment domain of human telomerase RNA to sustain catalytic activity in vitro". Nucleic Acids Research. 30 (20): 4470–80. PMID 12384594.
- Sood AK, Coffin J, Jabbari S, Buller RE, Hendrix MJ, Klingelhutz A (2003). "p53 null mutations are associated with a telomerase negative phenotype in ovarian carcinoma". Cancer Biology & Therapy. 1 (5): 511–7. S2CID 45381814.
- Antal M, Boros E, Solymosy F, Kiss T (February 2002). "Analysis of the structure of human telomerase RNA in vivo". Nucleic Acids Research. 30 (4): 912–20. PMID 11842102.