Tedavi yaklaşımlarında yeni bir dönem: Kodlamayan RNA’lar ve hastalıklar

Year 2013, Volume: 26 Issue: 1, 5 - 10, 30.09.2015

Zülfiye Akkaya Pervin Dinçer

Abstract

Yeni ribonükleik asit (RNA)’lerin bulunması ve işlevlerinin tanımlanmasıyla, RNA’ların canlı yaşamı için çok önemli süreçlerde rol oynadıkları belirlenmiştir. Özellikle insan genomunun %62’sini (ENCODE Consortium) kapsayan ncRNA (kodlamayan RNA)’ların hücresel savunmada, gelişimsel süreçlerde, farklılaşmada, DNA replikasyonunda, transkripsiyonda ve post-transkripsiyonel susturumda görev aldıkları gösterilmiştir. ncRNA’larda meydana gelen bozukluklar birçok hastalığa yol açmaktadır. İlişkili oldukları hastalıklardan bazıları kanserler, nörodejeneratif hastalıklar, immün yetmezlik hastalıkları ve kardiyovasküler hastalıklardır. Hastalıklardan sorumlu oldukları düşünülen ncRNA’lar, yeni tedavi yaklaşımlarında hem hedef hem de araç olarak görülmektedirler. İnsan genomundaki tüm ncRNA’ların işlevlerinin aydınlatılmasıyla yeni tedavi yaklaşımları geliştirilebilecektir. Bu derlemede, kodlanmayan RNA’ların çeşitleri, hastalıklarla olan ilişkileri, ve tanı-tedavi amaçlı kullanımlarıyla ilgili literatüre dayalı değerlendirme yapılmıştır.

Keywords

Kodlamayan RNA’lar, Hastalıklar, Tedavi

References

• 1. Taft RJ, Pheasant M, Mattick JS. The relationship between nonprotein-coding DNA and eukaryotic complexity. Bioessays 2007; 29:288–99. doi:10.1002/bies.20544
• 2. Birney E, Stamatoyannopoulos JA, Dutta A, et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 2007; 447:799–816. doi:10.1038/ nature05874
• 3. Carninci P, Kasukawa T, Katayama S, et al. The transcriptional landscape of the mammalian genome. Science 2005; 309:1559–63.
• 4. Mattick JS. A new paradigm for developmental biology. J Exp Biol 2007; 210:1526–47. doi:10.1242/jeb.005017
• 5. Kapranov P. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 2007; 316: 1484–8. doi:10.1126/science.1138341
• 6. Mette MF, Aufsatz W, van der Winden J, Matzke MA, Matzke AJ. Transcriptional silencing and promoter methylation triggered by double-stranded RNA. EMBO J 2000; 19:5194–201. doi:10.1093/ emboj/19.19.5194
• 7. Kanduri C, Whitehead J, Mohammad F. The long and the short of it: RNA-directed chromatin asymmetry in mammalian X-chromosome inactivation. FEBS Lett 2009; 583:857–64. doi:10.1016/j. febslet.2009.02.004
• 8. Voinnet O. Origin, biogenesis, and activity of plant microRNAs. Cell 2009; 136:669–87. doi:10.1016/j.cell.2009.01.046
• 9. Erson AE, Petty EM. MicroRNAs and in development and disease. Clin Genet 2008; 74:296-306. doi:10.1111/j.1399-0004.2008.01076.x
• 10. Wang G, Reinke V. A C. elegans Piwi, PRG-1, Regulates 21U-RNAs during Spermatogenesis. Curr Biol 2008; 18:861-7. doi:10.1016/j. cub.2008.05.009
• 11. Aravin AA, Sachidanandam R, Bourc’his D, et al. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell 2008; 6:785-99. doi:10.1016/j.molcel.2008.09.003
• 12. Malone C, Hannon G. Small RNAs as guardians of the genome. Cell 2009; 136:656–68. doi:10.1016/j.cell.2009.01.045
• 13. Bachellerie JP, Cavaille J, Huttenhofer A. The expanding snoRNA world. Biochemie 2002; 84: 775–90. doi:10.1016/S0300- 9084(02)01402-5
• 14. Simpson L, Sbicego S, Aphasizhev R. Uridine insertion/deletion RNA editing in trypanosome mitochondria: a complex business. RNA 2003; 9:265-76. doi:10.1261/rna.2178403
• 15. Reiner R, Ben-Asouli Y, Krilovetzky I, Jarrous N. A role for the catalytic ribonucleoprotein RNase P in RNA polymerase III transcription. Genes Dev 2006; 12: 1621–35. doi:10.1101/gad.386706
• 16. Marrone A, Dokal I. Dyskeratosis congenita: molecular insights into telomerase function, ageing and cancer. Expert Rev Mol Med 2007; 6: 1–23. doi:10.1017/S1462399404008671
• 17. Scheffer GL, Wijngaard PLJ, Flens MJ, et al. The drug resistancerelated protein Lrp is the human major vault protein. Nat Med 1995; 1 : 578–82. doi:10.1038/nm0695-578
• 18. Lerner MR, Boyle JA, Hardin JA, Steitz JA. Two novel classes of small ribonucleopro teins detected by antibodies associated with lupus erythematosus. Science 1981; 4480:400–2. doi:10.1126/ science.6164096
• 19. Christov CP, Trivier E, Krude T. Noncoding human Y RNAs are overexpressed in tumours and required for cell proliferation. Br J Cancer 2008; 5: 981–8. doi:10.1038/sj.bjc.6604254
• 20. Taft RJ, Simons C, Nahkuri S, et al. Nuclear-localized tiny RNAs are associated with transcription initiation and splice sites in metazoans. Nat Struct Mol Biol 2010; 17:1030-4. doi:10.1038/nsmb.1841
• 21. Dieci G, Fiorino G, Castelnuovo M, Teichmann M, Pagano A. The expanding RNA polymerase III transcriptome. Trends in Genet 2007; 23: 614–22. doi:10.1016/j.tig.2007.09.001
• 22. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet 2011; 18:12:861-74. doi:10.1038/nrg3074
• 23. He L, Hannon, G J. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004; 5:522–31. doi:10.1038/nrg1379
• 24. Aravin A A, Sachidanandam R, Girard A, Fejes-Toth K, Hannon G J. Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 2007; 316: 744–7. doi:10.1126/ science.1142612
• 25. Taft R J. Tiny RNAs associated with transcription start sites in animals. Nature Genet 2009; 41:572–8. doi:10.1038/ng.312
• 26. Kiss-László Z, Henry Y, Bachellerie J P, Caizergues-Ferrer M, Kiss T. Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs. Cell 1996; 85, 1077–88.
• 27. Mercer T R, Dinger M E, Mattick J S. Long non-coding RNAs insight into functions. Nature Rev Genet 2009; 10, 155–9. doi:10.1038/ nrg2521
• 28. Visone R, Croce CM. MiRNAs and cancer. Am J Pathol 2009; 174:1131–8. doi:10.2353/ajpath.2009.080794
• 29. Pang J, Kwok W, Chen Z, Ng H. Oncogenic role of microRNAs in brain tumors. Acta Neuropathol 2009; 117:599–611. doi:10.1007/ s00401-009-0525-0
• 30. Kocerha J, Kauppinen S, Wahlestedt C. MicroRNAs in CNS disorders. Neuromol Med 2009; 11:162-72. doi:10.1007/s12017-009-8066-1
• 31. Barringhaus K, Zamore P. MicroRNAs: regulating a change of heart. Circulation 2009; 119:2217-24. doi:10.1161/ CIRCULATIONAHA.107.715839
• 32. Davalos V, Moutinho C, Villanueva A, et al. Dynamic epigenetic regulation of the microRNA 200 family mediates epithelial and mesenchymal transitions in human tumorigenesis. Oncogene 2012; 19:2062-74.
• 33. Calin G, Dumitru C D, Shimizu M, et al. Frequent deletions and downregulation of micro RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002; 99: 15524–29. doi: 10.1073/pnas.242606799
• 34. Sun G, Wang Y, Sun L, et al. Clinical significance of Hiwi gene expression in gliomas. Brain Res 2011; 1373: 183–8. doi:10.1016/j. brainres.2010.11.097
• 35. Liu X, Sun Y, Guo J, et al. Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells. Int J Cancer 2006; 118: 1922–9. doi:10.1002/ijc.21575
• 36. Lee T I, Jenner R G, Boyer L A, Guenther M G, Levine S S. Control of developmental regulators by polycomb in human embryonic stem cells. Cell 2006; 125: 301–13. doi:10.1016/j.cell.2006.02.043
• 37. Liao J, Yu L, Mei Y, Guarnera M, Shen J. Small nucleolar RNA signatures as biomarkers for non‑small‑cell lung cancer. Mol Cancer 2010; 9: 198. doi:10.1186/1476-4598-9-198
• 38. Dong XY, Guo P, Boyd J, Sun X, Li Q. Implication of snoRNA U50 in human breast cancer. J Genet Genomics 2009;36,: 447-54.doi:10.1016/ S1673-8527(08)60134-4
• 39. Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT. Growth arrest in human T-cells is controlled by the noncoding RNA growth-arrest-specific transcript 5 (GAS5). J Cell Sci 2008; 121: 939-46. doi:10.1242/jcs.024646
• 40. Calin GA, Liu CG, Ferracin M, et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell 2007; 12: 215–29. doi:10.1016/j.ccr.2007.07.027
• 41. Gehrke S, Imai Y, Sokol N, Lu B. Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature 2010; 466: 637–41. doi:10.1038/nature09191
• 42. Starczynowski DT, Kuchenbauer F, Argiropoulos B, et al. Identification of miR‑145 and miR‑146a as mediators of the 5q- syndrome phenotype. Nat Med 2010; 16: 49–58.
• 43. Horsthemke B, Wagstaff J. Mechanisms of imprinting of the PraderWilli/Angelman region. Am J Med Genet A 2008; 146 A: 2041–52. doi:10.1002/ajmg.a.32364
• 44. Haramati S, Chapnik E, Sztainberg Y, et al. miRNA malfunction causes spinal motor neuron disease. Proc Natl Acad Sci USA 2010; 107: 13111–6. doi:10.1073/pnas.1006151107
• 45. Thum T, Gross C, Fiedler J, et al. MicroRNA‑21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 2008; 456: 980–4. doi:10.1038/nature07511
• 46. Urdinguio RG, Fernandez AF, Lopez-Nieva P, et al. Disrupted microRNA expression caused by Mecp2 loss in a mouse model of Rett syndrome. Epigenetics 2010; 5: 656-63. doi:10.4161/epi.5.7.13055
• 47. Gatto S, Della Ragione F, Cimmino A, Strazzullo M, Fabbri M. Epigenetic alteration of microRNAs in DNMT3B‑mutated patients of ICF syndrome. Epigenetics 2010; 5: 427–43. doi:10.4161/ epi.5.5.11999
• 48. Brest P, Lapaquette P, Souidi M, et al. A synonymous variant in IRGM alters a binding site for miR196 and causes deregulation of IRGMdependent xenophagy in Crohn’s disease. Nat Genet 2011; 43: 242–5. doi:10.1038/ng.762
• 49. Eggermann T. Silver-Russell and Beckwith– Wiedemann syndromes: opposite (epi)mutations in 11p15 result in opposite clinical pictures. Horm Res 2009; 71: (Suppl. 2): 30–5. doi:10.1159/000192433
• 50. Lewis MA, Quint E, Glazier AM, et al. An ENU-induced mutation of miR‑96 associated with progressive hearing loss in mice. Nat Genet 2009; 41: 614–8. doi:10.1038/ng.369
• 51. Hébert S S, Horré K, Nicolaï L, Papadopoulou A S, Mandemakers W. Loss of microRNA cluster miR‑29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/β-secretase expression. Proc Natl Acad Sci USA 2008; 105: 6415–20.
• 52. Faghihi MA, Modarresi F, Khalil AM, et al. Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat Med 2008; 14: 723–30. doi:10.1038/ nm1784
• 53. Kuhn D E, Nuovo G J, Terry A V Jr, Martin M M, Malana G E. Chromosome 21‑derived microRNAs provide an etiological basis for aberrant protein expression in human Down syndrome brains. J Biol Chem 2010; 285: 1529–43. doi:10.1074/jbc.M109.033407
• 54. Pauley K M, Cha S. miRNA‑146a in rheumatoid arthritis: a new therapeutic strategy. Immunotherapy 2011; 3:829–31. doi:10.2217/ imt.11.70
• 55. Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature 2005; 435:834–8. doi:10.1038/nature03702
• 56. Cortez MA, Calin GA. MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther 2009; 9:703–11. doi:10.1517/14712590902932889
• 57. Swanton C, Caldas C. Molecular classification of solid tumours: towards pathway-driven therapeutics. Br J Cancer 2009; 100: 1517– 22. doi:10.1038/sj.bjc.6605031
• 58. Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS. Non-coding RNAs: regulators of disease. J Pathol 2010; 220:126-39.
• 59. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 2001; 411:494–8. doi:10.1038/35078107
• 60. Lee NS, Dohjima T, Bauer G, et al. Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat Biotechnol 2002; 20:500–5.
• 61. Whitehead K, Langer R, Anderson DG. Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 2009; 8:129–38. doi:10.1038/nrd2742
• 62. Wang V, Wu W. MicroRNA-based therapeutics for cancer. Bio Drugs 2009; 23:15–23. doi:10.2165/00063030-200923010-00002
• 63. Krutzfeldt J, Rajewsky N, Braich R. Silencing of microRNAs in vivo with ‘antagomirs’. Nature 2005; 438:685–9.
• 64. Ma L, Reinhardt F, Pan E, et al. Therapeutic silencing of miR10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol 2010; 28: 341–7. doi:10.1038/nbt.1618
• 65. Elmen J, Lindow M, Schutz S. LNA-mediated microRNA silencing in non-human primates. Nature 2008; 452: 896–9.
• 66. Ma L, Young J, Prabhala H, et al. miR‑9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol 2010; 12: 247–56. doi:10.1038/ncb2024
• 67. Saito Y, Liang G, Egger G, et al. Specific activation of microRNA127 with downregulation of the proto-oncogene BCL6 by chromatinmodifying drugs in human cancer cells. Cancer Cell 2006; 9:435–43. doi:10.1016/j.ccr.2006.04.020
• 68. Tsai M C, Manor O, Wan Y, et al. Long noncoding RNA as a modular scaffold of histone modification complexes. Science 2010; 329: 689– 93. doi:10.1126/science.1192002
• 69. Medina P P, Nolde M, Slack F J. OncomiR addiction in an in vivo model of microRNA-21‑induced pre‑B‑cell lymphoma. Nature 2010; 467: 86–90. doi:10.1038/nature09284
• 70. Ebert MS, Neilson JR, Sharp PA. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 2007; 4:721-6. doi:10.1038/nmeth1079