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TERC olarak da bilinen telomeraz RNA bileşeni ökaryotlarda bulunan ve telomerazın bir bileşeni olan Kodlamayan RNA'dır. TERC, telomeraz ile telomer replikasyonu (ters transkripsiyon) için bir kalıp görevi görür. Telomeraz RNA'ları dizi ve yapı açısından omurgalılar, ve mayalar arasında büyük farklılıklar gösterir, ancak şablon dizisine yakın bir 5 'sahte düğüm yapıyı paylaşmaktadırlar. Omurgalı telomeraz RNA'larının, 3 'H / ACA snoRNA benzeri alanı vardır.
İşlev
Telomeraz, telomer tekrarını TTAGGG telomere tekrar ekleyerek muhafaza eden bir ribonükleoprotein polimerazdır. Bu tekrar ökaryotlarda farklılık gösterir. Bu enzim ters transkriptaz aktivitesine sahip bir protein bileşeninden (TERT) ve telomer tekrarında bir kalıp görevi gören bu gen tarafından kodlanan bir RNA bileşeninden oluşur. CCCUAA, omurgalıların TERC dizisinin 50. konumuna yakın bir yerde bulundu ve kalıp olarak kullanılır. Telomeraz ekspresyonu hücresel yaşlanmada rol oynar ve telomerlerin aşamalı olarak kısalmasına neden olur. Ancak, postnatal somatik hücrelerde normalde bastırılır. Somatik hücrelerde telomeraz ekspresyonunun serbestleştirilmesi, onkogenezde (tümör oluşumu) rol oynayabilir. Fare çalışmaları, telomer tekrarının sentezinin çift zincir kopmalarında oluşabileceğini, telomerazın kromozom onarımına da katkıda bulunduğunu ortaya koymaktadır. TERC'nin homologları virüslerinde de bulunur.
Klinik Önemi
Bu gendeki mutasyonlar, otozomal dominant ’a neden olur ve ayrıca bazı aplastik anemi vakaları ile ilişkili olabilir. (Konjenital Diskeratoz: Deri pigmentasyonu, atrofik tırnaklar, lökoplaki ve kemik iliği yetersizliği ile karakterize, nadir rastlanan, dejeneratif bir bozukluktur.)
Kaynakça
- ^ Feng J, Funk WD, Wang SS, Weinrich SL, Avilion AA, Chiu CP, Adams RR, Chang E, Allsopp RC, Yu J (Eylül 1995). "The RNA component of human telomerase". Science. 269 (5228). ss. 1236-41. doi:10.1126/science.7544491. (PMID) 7544491.
- ^ Jády BE, Richard P, Bertrand E, Kiss T (Şubat 2006). "Cell Cycle-dependent Recruitment of Telomerase RNA and Cajal Bodies to Human Telomeres". Mol. Biol. Cell. 17 (2). ss. 944-54. doi:10.1091/mbc.E05-09-0904. (PMC) 1356602 $2. (PMID) 16319170.
- ^ McCormick-Graham, M; Romero DP (1995). "Ciliate telomerase RNA structural features". Nucleic Acids Res. 23 (7). ss. 1091–1097. doi:10.1093/nar/23.7.1091. (PMC) 306816 $2. (PMID) 7739888.
- ^ Lingner, J; Hendrick LL; Cech TR (1994). "Telomerase RNAs of different ciliates have a common secondary structure and a permuted template". Genes Dev. 8 (16). ss. 1984–1998. doi:10.1101/gad.8.16.1984. (PMID) 7958872.
- ^ Theimer CA, Feigon J (2006). "Structure and function of telomerase RNA". Curr. Opin. Struct. Biol. 16 (3). ss. 307-18. doi:10.1016/j.sbi.2006.05.005. (PMID) 16713250.
- ^ a b "Entrez Gene: TERC telomerase RNA component". 8 Mart 2010 tarihinde kaynağından .
- ^ Fragnet, L; Kut E; Rasschaert D (2005). "Comparative functional study of the viral telomerase RNA based on natural mutations". J Biol Chem. 280 (25). ss. 23502–23515. doi:10.1074/jbc.M501163200. (PMID) 15811851.
Notlar
- de Lange T, Jacks T (1999). "For better or worse? Telomerase inhibition and cancer". Cell. 98 (3). ss. 273-5. doi:10.1016/S0092-8674(00)81955-8. (PMID) 10458601.
- Marrone A, Dokal I (2007). "Dyskeratosis congenita: molecular insights into telomerase function, ageing and cancer". Expert Reviews in Molecular Medicine. 6 (26). ss. 1-23. doi:10.1017/S1462399404008671. (PMID) 15613268.
- Yamaguchi H (2007). "Mutations of telomerase complex genes linked to bone marrow failures". Journal of Nippon Medical School = Nihon Ika Daigaku zasshi. 74 (3). ss. 202-9. doi:10.1272/jnms.74.202. (PMID) 17625368.
- Zaug AJ, Linger J, Cech TR (1996). "Method for determining RNA 3' ends and application to human telomerase RNA". Nucleic Acids Res. 24 (3). ss. 532-3. doi:10.1093/nar/24.3.532. (PMC) 145649 $2. (PMID) 8602368.
- Soder AI, Hoare SF, Muire S, Balmain A, Parkinson E, Keith W (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). ss. 293-4. doi:10.1006/geno.1997.4621. (PMID) 9143511.
- Zhao JQ, Hoare SF, McFarlane R, Muir S, Parkinson EK, Black DM, Keith WN (1998). "Cloning and characterization of human and mouse telomerase RNA gene promoter sequences". Oncogene. 16 (10). ss. 1345-50. doi:10.1038/sj.onc.1201892. (PMID) 9546436.
- Mitchell JR, Wood E, Collins K (1999). "A telomerase component is defective in the human disease dyskeratosis congenita". Nature. 402 (6761). ss. 551-5. doi:10.1038/990141. (PMID) 10591218.
- Chen JL, Blasco MA, Greider CW (2000). "Secondary structure of vertebrate telomerase RNA". Cell. 100 (5). ss. 503-14. doi:10.1016/S0092-8674(00)80687-X. (PMID) 10721988.
- Wong KK, Chang S, Weiler SR, Weiler SR, Ganesan S, Chaudhuri J, Zhu C, Artandi SE, Rudolph KL (2000). "Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation". Nat. Genet. 26 (1). ss. 85-8. doi:10.1038/79232. (PMID) 10973255.
- Mitchell JR, Collins K (2000). "Human telomerase activation requires two independent interactions between telomerase RNA and telomerase reverse transcriptase". Mol. Cell. 6 (2). ss. 361-71. doi:10.1016/S1097-2765(00)00036-8. (PMID) 10983983.
- Imoto I, Pimkhaokham A, Fukuda Y, Yang Z, Shimada Y, Nomura N, Hirai H, Imamura M, Inazawa J (2001). "SNO is a probable target for gene amplification at 3q26 in squamous-cell carcinomas of the esophagus". Biochem. Biophys. Res. Commun. 286 (3). ss. 559-65. doi:10.1006/bbrc.2001.5428. (PMID) 11511096.
- Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I (2001). "The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita". Nature. 413 (6854). ss. 432-5. doi:10.1038/35096585. (PMID) 11574891.
- Pruzan R, Pongracz K, Gietzen K, Wallweber G, Gryaznov S (2002). "Allosteric inhibitors of telomerase: oligonucleotide N3′→P5′ phosphoramidates". Nucleic Acids Res. 30 (2). ss. 559-68. doi:10.1093/nar/30.2.559. (PMC) 99832 $2. (PMID) 11788719.
- Zhang RG, Zhang RP, Wang XW, Xie H (2004). "Effects of cisplatin on telomerase activity and telomere length in BEL-7404 human hepatoma cells". Cell Res. 12 (1). ss. 55-62. doi:10.1038/sj.cr.7290110. (PMID) 11942411.
- Yang Y, Chen Y, Zhang C, Huang H, Weissman SM (2002). "Nucleolar localization of hTERT protein is associated with telomerase function". Exp. Cell Res. 277 (2). ss. 201-9. doi:10.1006/excr.2002.5541. (PMID) 12083802.
- Chang JT, Chen YL, Yang HT, Chen C, Cheng A (2002). "Differential regulation of telomerase activity by six telomerase subunits". Eur. J. Biochem. 269 (14). ss. 3442-50. doi:10.1046/j.1432-1033.2002.03025.x. (PMID) 12135483.
- Gavory G, Farrow M, Balasubramanian S (2002). "Minimum length requirement of the alignment domain of human telomerase RNA to sustain catalytic activity in vitro". Nucleic Acids Res. 30 (20). ss. 4470-80. doi:10.1093/nar/gkf575. (PMC) 137139 $2. (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 Biol. Ther. 1 (5). ss. 511-7. doi:10.4161/cbt.1.5.167. (PMID) 12496479.
- Antal, M; Boros E; Solymosy F; Kiss T (2002). "Analysis of the structure of human telomerase RNA in vivo". Nucleic Acids Res. 30 (4). ss. 912–920. doi:10.1093/nar/30.4.912. (PMC) 100349 $2. (PMID) 11842102.
Dış bağlantılar
- GeneReviews/NCBI/NIH/UW entry on Dyskeratosis Congenita4 Mart 2010 tarihinde Wayback Machine sitesinde .
- GeneReviews/NCBI/NIH/UW entry on Pulmonary Fibrosis, Familial27 Eylül 2009 tarihinde Wayback Machine sitesinde .
- EntrezGene page for TERC8 Mart 2010 tarihinde Wayback Machine sitesinde .
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TERC olarak da bilinen telomeraz RNA bileseni okaryotlarda bulunan ve telomerazin bir bileseni olan Kodlamayan RNA dir TERC telomeraz ile telomer replikasyonu ters transkripsiyon icin bir kalip gorevi gorur Telomeraz RNA lari dizi ve yapi acisindan omurgalilar ve mayalar arasinda buyuk farkliliklar gosterir ancak sablon dizisine yakin bir 5 sahte dugum yapiyi paylasmaktadirlar Omurgali telomeraz RNA larinin 3 H ACA snoRNA benzeri alani vardir IslevTelomeraz telomer tekrarini TTAGGG telomere tekrar ekleyerek muhafaza eden bir ribonukleoprotein polimerazdir Bu tekrar okaryotlarda farklilik gosterir Bu enzim ters transkriptaz aktivitesine sahip bir protein bileseninden TERT ve telomer tekrarinda bir kalip gorevi goren bu gen tarafindan kodlanan bir RNA bileseninden olusur CCCUAA omurgalilarin TERC dizisinin 50 konumuna yakin bir yerde bulundu ve kalip olarak kullanilir Telomeraz ekspresyonu hucresel yaslanmada rol oynar ve telomerlerin asamali olarak kisalmasina neden olur Ancak postnatal somatik hucrelerde normalde bastirilir Somatik hucrelerde telomeraz ekspresyonunun serbestlestirilmesi onkogenezde tumor olusumu rol oynayabilir Fare calismalari telomer tekrarinin sentezinin cift zincir kopmalarinda olusabilecegini telomerazin kromozom onarimina da katkida bulundugunu ortaya koymaktadir TERC nin homologlari viruslerinde de bulunur Klinik OnemiBu gendeki mutasyonlar otozomal dominant a neden olur ve ayrica bazi aplastik anemi vakalari ile iliskili olabilir Konjenital Diskeratoz Deri pigmentasyonu atrofik tirnaklar lokoplaki ve kemik iligi yetersizligi ile karakterize nadir rastlanan dejeneratif bir bozukluktur Kaynakca Feng J Funk WD Wang SS Weinrich SL Avilion AA Chiu CP Adams RR Chang E Allsopp RC Yu J Eylul 1995 The RNA component of human telomerase Science 269 5228 ss 1236 41 doi 10 1126 science 7544491 PMID 7544491 Jady BE Richard P Bertrand E Kiss T Subat 2006 Cell Cycle dependent Recruitment of Telomerase RNA and Cajal Bodies to Human Telomeres Mol Biol Cell 17 2 ss 944 54 doi 10 1091 mbc E05 09 0904 PMC 1356602 2 PMID 16319170 McCormick Graham M Romero DP 1995 Ciliate telomerase RNA structural features Nucleic Acids Res 23 7 ss 1091 1097 doi 10 1093 nar 23 7 1091 PMC 306816 2 PMID 7739888 Lingner J Hendrick LL Cech TR 1994 Telomerase RNAs of different ciliates have a common secondary structure and a permuted template Genes Dev 8 16 ss 1984 1998 doi 10 1101 gad 8 16 1984 PMID 7958872 Theimer CA Feigon J 2006 Structure and function of telomerase RNA Curr Opin Struct Biol 16 3 ss 307 18 doi 10 1016 j sbi 2006 05 005 PMID 16713250 a b Entrez Gene TERC telomerase RNA component 8 Mart 2010 tarihinde kaynagindan Fragnet L Kut E Rasschaert D 2005 Comparative functional study of the viral telomerase RNA based on natural mutations J Biol Chem 280 25 ss 23502 23515 doi 10 1074 jbc M501163200 PMID 15811851 Notlarde Lange T Jacks T 1999 For better or worse Telomerase inhibition and cancer Cell 98 3 ss 273 5 doi 10 1016 S0092 8674 00 81955 8 PMID 10458601 Marrone A Dokal I 2007 Dyskeratosis congenita molecular insights into telomerase function ageing and cancer Expert Reviews in Molecular Medicine 6 26 ss 1 23 doi 10 1017 S1462399404008671 PMID 15613268 Yamaguchi H 2007 Mutations of telomerase complex genes linked to bone marrow failures Journal of Nippon Medical School Nihon Ika Daigaku zasshi 74 3 ss 202 9 doi 10 1272 jnms 74 202 PMID 17625368 Zaug AJ Linger J Cech TR 1996 Method for determining RNA 3 ends and application to human telomerase RNA Nucleic Acids Res 24 3 ss 532 3 doi 10 1093 nar 24 3 532 PMC 145649 2 PMID 8602368 Soder AI Hoare SF Muire S Balmain A Parkinson E Keith W 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 ss 293 4 doi 10 1006 geno 1997 4621 PMID 9143511 Zhao JQ Hoare SF McFarlane R Muir S Parkinson EK Black DM Keith WN 1998 Cloning and characterization of human and mouse telomerase RNA gene promoter sequences Oncogene 16 10 ss 1345 50 doi 10 1038 sj onc 1201892 PMID 9546436 Mitchell JR Wood E Collins K 1999 A telomerase component is defective in the human disease dyskeratosis congenita Nature 402 6761 ss 551 5 doi 10 1038 990141 PMID 10591218 Chen JL Blasco MA Greider CW 2000 Secondary structure of vertebrate telomerase RNA Cell 100 5 ss 503 14 doi 10 1016 S0092 8674 00 80687 X PMID 10721988 Wong KK Chang S Weiler SR Weiler SR Ganesan S Chaudhuri J Zhu C Artandi SE Rudolph KL 2000 Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation Nat Genet 26 1 ss 85 8 doi 10 1038 79232 PMID 10973255 Mitchell JR Collins K 2000 Human telomerase activation requires two independent interactions between telomerase RNA and telomerase reverse transcriptase Mol Cell 6 2 ss 361 71 doi 10 1016 S1097 2765 00 00036 8 PMID 10983983 Imoto I Pimkhaokham A Fukuda Y Yang Z Shimada Y Nomura N Hirai H Imamura M Inazawa J 2001 SNO is a probable target for gene amplification at 3q26 in squamous cell carcinomas of the esophagus Biochem Biophys Res Commun 286 3 ss 559 65 doi 10 1006 bbrc 2001 5428 PMID 11511096 Vulliamy T Marrone A Goldman F Dearlove A Bessler M Mason PJ Dokal I 2001 The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita Nature 413 6854 ss 432 5 doi 10 1038 35096585 PMID 11574891 Pruzan R Pongracz K Gietzen K Wallweber G Gryaznov S 2002 Allosteric inhibitors of telomerase oligonucleotide N3 P5 phosphoramidates Nucleic Acids Res 30 2 ss 559 68 doi 10 1093 nar 30 2 559 PMC 99832 2 PMID 11788719 Zhang RG Zhang RP Wang XW Xie H 2004 Effects of cisplatin on telomerase activity and telomere length in BEL 7404 human hepatoma cells Cell Res 12 1 ss 55 62 doi 10 1038 sj cr 7290110 PMID 11942411 Yang Y Chen Y Zhang C Huang H Weissman SM 2002 Nucleolar localization of hTERT protein is associated with telomerase function Exp Cell Res 277 2 ss 201 9 doi 10 1006 excr 2002 5541 PMID 12083802 Chang JT Chen YL Yang HT Chen C Cheng A 2002 Differential regulation of telomerase activity by six telomerase subunits Eur J Biochem 269 14 ss 3442 50 doi 10 1046 j 1432 1033 2002 03025 x PMID 12135483 Gavory G Farrow M Balasubramanian S 2002 Minimum length requirement of the alignment domain of human telomerase RNA to sustain catalytic activity in vitro Nucleic Acids Res 30 20 ss 4470 80 doi 10 1093 nar gkf575 PMC 137139 2 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 Biol Ther 1 5 ss 511 7 doi 10 4161 cbt 1 5 167 PMID 12496479 Antal M Boros E Solymosy F Kiss T 2002 Analysis of the structure of human telomerase RNA in vivo Nucleic Acids Res 30 4 ss 912 920 doi 10 1093 nar 30 4 912 PMC 100349 2 PMID 11842102 Dis baglantilarGeneReviews NCBI NIH UW entry on Dyskeratosis Congenita4 Mart 2010 tarihinde Wayback Machine sitesinde GeneReviews NCBI NIH UW entry on Pulmonary Fibrosis Familial27 Eylul 2009 tarihinde Wayback Machine sitesinde EntrezGene page for TERC8 Mart 2010 tarihinde Wayback Machine sitesinde