端粒酶RNA組分
位於3號人類染色體的基因
端粒酶RNA組分(英語:telomerase RNA component,缩写为TERC)或称端粒酶RNA,是一種真核生物的非編碼RNA(ncRNA)。它是端粒酶的組成成分之一——端粒酶用它來延長端粒[2][3]。端粒酶RNA在DNA複製過程中,爲端粒的逆轉錄過程提供模板。酵母、纖毛蟲、脊椎動物的端粒酶RNA的序列和結構都有很大不同。不過,它們的5'端靠近模板序列處,都有一個假結結構。脊椎動物端粒酶RNA的3'端有一個與snoRNA(核仁RNA)類似的結構域[4][5][6]。
端粒酶RNA組分 Telomerase RNA component (TERC) | |||
---|---|---|---|
标识 | |||
代号 | TERC; DKCA1; PFBMFT2; SCARNA19; TR; TRC3; hTR | ||
扩展标识 | 遗传学:602322 鼠基因:109558 GeneCards: TERC Gene | ||
直系同源体 | |||
物种 | 人类 | 小鼠 | |
Entrez | 7012 | 21748 | |
Ensembl | ENSG00000200182 | ENSMUSG00000064796 | |
UniProt | n/a | n/a | |
mRNA序列 | n/a | n/a | |
蛋白序列 | n/a | n/a | |
基因位置 |
Chr 3: 169.48 – 169.48 Mb |
Chr 3: 96.22 – 96.22 Mb | |
PubMed查询 | [1] | [2] | |
脊椎動物端粒酶RNA | |
---|---|
识别符 | |
代号 | Telomerase-vert |
Rfam | RF00024 |
其他数据 | |
RNA类型 | 基因 |
域 | 真核、病毒 |
纖毛蟲端粒酶RNA | |
---|---|
识别符 | |
代号 | Telomerase-cil |
Rfam | RF00025 |
其他数据 | |
RNA类型 | 基因 |
域 | 真核生物 |
釀酒酵母端粒酶RNA | |
---|---|
识别符 | |
代号 | Sacc telomerase |
Rfam | RF01050 |
其他数据 | |
RNA类型 | 基因 |
域 | 真核生物 |
功能
端粒酶係一類核糖核蛋白聚合酶。它通過給端粒加上重複序列來維持其長度。該重複序列在不同真核生物間有很大不同(具體可參見端粒條目中的比較表)。端粒酶除RNA外,還含有蛋白質組分(TERT,端粒酶逆轉錄酶)。端粒酶的蛋白質組分具有逆轉錄酶的活性。端粒酶的RNA組分,即端粒酶RNA,充當逆轉錄的模板。在脊椎動物端粒酶序列中,作爲模板的CCCUAA序列在50位左右出現。端粒酶的表達在細胞衰老中扮演重要角色,在成熟體細胞中,端粒酶的表达通常處於受抑制狀態,因而端粒會不斷縮短。體細胞的端粒酶表达失調可能會誘發癌變。對小鼠的研究表明,端粒酶亦參與染色體修復,因爲在雙鏈都損壞的情況下,可能需要從頭合成端粒重複序列[7]。在皰疹病毒亦發現了與端粒酶RNA同源的RNA[8]。
臨床意義
参考文献
- ^ PDB 1ymo; Theimer CA, Blois CA, Feigon J. Structure of the human telomerase RNA pseudoknot reveals conserved tertiary interactions essential for function.. Mol Cell. 2005, 17 (5): 671–82. PMID 15749017. doi:10.1016/j.molcel.2005.01.017.
- ^ Feng J, Funk WD, Wang SS, Weinrich SL, Avilion AA, Chiu CP, Adams RR, Chang E, Allsopp RC, Yu J. The RNA component of human telomerase. Science. September 1995, 269 (5228): 1236–41. PMID 7544491. doi:10.1126/science.7544491.
- ^ Jády BE, Richard P, Bertrand E, Kiss T. Cell Cycle-dependent Recruitment of Telomerase RNA and Cajal Bodies to Human Telomeres. Mol. Biol. Cell. February 2006, 17 (2): 944–54. PMC 1356602 . PMID 16319170. doi:10.1091/mbc.E05-09-0904.
- ^ McCormick-Graham, M; Romero DP. Ciliate telomerase RNA structural features. Nucleic Acids Res. 1995, 23 (7): 1091–1097. PMC 306816 . PMID 7739888. doi:10.1093/nar/23.7.1091.
- ^ Lingner, J; Hendrick LL; Cech TR. Telomerase RNAs of different ciliates have a common secondary structure and a permuted template. Genes Dev. 1994, 8 (16): 1984–1998. PMID 7958872. doi:10.1101/gad.8.16.1984.
- ^ Theimer CA, Feigon J. Structure and function of telomerase RNA. Curr. Opin. Struct. Biol. 2006, 16 (3): 307–18. PMID 16713250. doi:10.1016/j.sbi.2006.05.005.
- ^ 7.0 7.1 Entrez Gene: TERC telomerase RNA component. (原始内容存档于2010-03-08).
- ^ Fragnet, L; Kut E; Rasschaert D. Comparative functional study of the viral telomerase RNA based on natural mutations. J Biol Chem. 2005, 280 (25): 23502–23515. PMID 15811851. doi:10.1074/jbc.M501163200.
拓展閱讀
- de Lange T, Jacks T. For better or worse? Telomerase inhibition and cancer. Cell. 1999, 98 (3): 273–5. PMID 10458601. doi:10.1016/S0092-8674(00)81955-8.
- Marrone A, Dokal I. Dyskeratosis congenita: molecular insights into telomerase function, ageing and cancer. Expert Reviews in Molecular Medicine. 2007, 6 (26): 1–23. PMID 15613268. doi:10.1017/S1462399404008671.
- Yamaguchi H. Mutations of telomerase complex genes linked to bone marrow failures. Journal of Nippon Medical School = Nihon Ika Daigaku zasshi. 2007, 74 (3): 202–9. PMID 17625368. doi:10.1272/jnms.74.202.
- Zaug AJ, Linger J, Cech TR. Method for determining RNA 3' ends and application to human telomerase RNA. Nucleic Acids Res. 1996, 24 (3): 532–3. PMC 145649 . PMID 8602368. doi:10.1093/nar/24.3.532.
- Soder AI, Hoare SF, Muire S, et al. Mapping of the gene for the mouse telomerase RNA component, Terc, to chromosome 3 by fluorescence in situ hybridization and mouse chromosome painting. Genomics. 1997, 41 (2): 293–4. PMID 9143511. doi:10.1006/geno.1997.4621.
- Zhao JQ, Hoare SF, McFarlane R, et al. Cloning and characterization of human and mouse telomerase RNA gene promoter sequences. Oncogene. 1998, 16 (10): 1345–50. PMID 9546436. doi:10.1038/sj.onc.1201892.
- Mitchell JR, Wood E, Collins K. A telomerase component is defective in the human disease dyskeratosis congenita. Nature. 1999, 402 (6761): 551–5. PMID 10591218. doi:10.1038/990141.
- Chen JL, Blasco MA, Greider CW. Secondary structure of vertebrate telomerase RNA. Cell. 2000, 100 (5): 503–14. PMID 10721988. doi:10.1016/S0092-8674(00)80687-X.
- Wong KK, Chang S, Weiler SR, et al. Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nat. Genet. 2000, 26 (1): 85–8. PMID 10973255. doi:10.1038/79232.
- Mitchell JR, Collins K. Human telomerase activation requires two independent interactions between telomerase RNA and telomerase reverse transcriptase. Mol. Cell. 2000, 6 (2): 361–71. PMID 10983983. doi:10.1016/S1097-2765(00)00036-8.
- Imoto I, Pimkhaokham A, Fukuda Y, et al. SNO is a probable target for gene amplification at 3q26 in squamous-cell carcinomas of the esophagus. Biochem. Biophys. Res. Commun. 2001, 286 (3): 559–65. PMID 11511096. doi:10.1006/bbrc.2001.5428.
- Vulliamy T, Marrone A, Goldman F, et al. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature. 2001, 413 (6854): 432–5. PMID 11574891. doi:10.1038/35096585.
- Pruzan R, Pongracz K, Gietzen K, et al. Allosteric inhibitors of telomerase: oligonucleotide N3′→P5′ phosphoramidates. Nucleic Acids Res. 2002, 30 (2): 559–68. PMC 99832 . PMID 11788719. doi:10.1093/nar/30.2.559.
- Zhang RG, Zhang RP, Wang XW, Xie H. Effects of cisplatin on telomerase activity and telomere length in BEL-7404 human hepatoma cells. Cell Res. 2004, 12 (1): 55–62. PMID 11942411. doi:10.1038/sj.cr.7290110.
- Yang Y, Chen Y, Zhang C, et al. Nucleolar localization of hTERT protein is associated with telomerase function. Exp. Cell Res. 2002, 277 (2): 201–9. PMID 12083802. doi:10.1006/excr.2002.5541.
- Chang JT, Chen YL, Yang HT, et al. Differential regulation of telomerase activity by six telomerase subunits. Eur. J. Biochem. 2002, 269 (14): 3442–50. PMID 12135483. doi:10.1046/j.1432-1033.2002.03025.x.
- Gavory G, Farrow M, Balasubramanian S. Minimum length requirement of the alignment domain of human telomerase RNA to sustain catalytic activity in vitro. Nucleic Acids Res. 2002, 30 (20): 4470–80. PMC 137139 . PMID 12384594. doi:10.1093/nar/gkf575.
- Sood AK, Coffin J, Jabbari S, et al. p53 null mutations are associated with a telomerase negative phenotype in ovarian carcinoma. Cancer Biol. Ther. 2003, 1 (5): 511–7. PMID 12496479. doi:10.4161/cbt.1.5.167.
- Antal, M; Boros E; Solymosy F; Kiss T. Analysis of the structure of human telomerase RNA in vivo. Nucleic Acids Res. 2002, 30 (4): 912–920. PMC 100349 . PMID 11842102. doi:10.1093/nar/30.4.912.