A Gene Expression Regulator: miRNA

Yıl 2015, Cilt: 24 Sayı: 4, 472 - 493, 15.09.2015

Figen Güzelgül , Kıymet Aksoy

https://doi.org/10.17827/aktd.95263

Cited By: 3

Öz

MicroRNAs (miRNA) binding to target mRNAs and having function in regulating gene expression are of 18-25 nucleotides in length and take place in the class of non-coding RNAs. Although aproximately 1900 human miRNA types have been identified so far, quite little is known about their biological functions. In some studies, it is shown that miRNA expression levels are important for many biological functions such as cell proliferation, differentiation, apoptosis and metabolism. Recent studies have pointed out that miRNAs have been used as diagnosis and prognosis biomarker in many human diseases including cancer, viral diseases, cardiovascular disorders and metabolic distrubance.Such as a miRNA type’s regulating more than one mRNA expression levels, a mRNA level has been regulated by numbers of miRNA types. Since changing the expression level of a miRNA type effects the whole metabolism, it is required to have cell-specific miRNAs. In the event of cell type- specific miRNAs are having found, it is expected that the general metabolism is better understood and, moreover, miRNAs are used more effectively in diagnosis and treatment of diseases.

Anahtar Kelimeler

Noncoding RNA, miRNA, Mrna

Bir Gen İfade Düzenleyicisi miRNA

Öz

Hedef mRNA’lara bağlanarak gen ifadesinin düzenlenmesinde işlev gören mikroRNA’lar (miRNA) 18-25 nükleotit uzunluğunda olup kısa kodlanmayan RNA sınıfında yer almaktadırlar. İnsanlarda yaklaşık 1900 miRNA tipi tanımlanmış olmasına rağmen şimdiye kadar biyolojik işlevleri hakkında bilinenler oldukça azdır. Bazı çalışmalarda hücrelerin proliferasyon, farklılaşma, apoptozis ve metabolizma gibi biyolojik işlevlerdemiRNA’ların ekspresyon seviyelerinin önemli olduğu gösterilmiştir. Son zamanlardaki çalışmalarda miRNA’ların kanser, viral hastalıklar, kardiovasküler hastalıklar ve metabolik bozuklukları da içine alan birçok hastalıkta tanı ve prognozda kullanılabileceği belirtilmiştir. Bir miRNA tipinin birden fazla mRNA’nın ekspresyon seviyesini düzenlediği gibi, bir mRNA ekspresyonu birden fazla miRNA tipi tarafından düzenlenebilmektedir. Bir miRNA tipinin ekspresyon düzeyini değiştirmek tüm metabolizmayı etkileyebileceği için hücre tipine özgü miRNA’ların bulunması gerekmektedir. Hücre tiplerine özgü miRNA’ların bulunması halinde genel metabolizmanın daha iyi anlaşılması ve hatta hastalıkların tanı ve tedavisinde miRNA’ların etkin olarak kullanılması beklenmektedir.

Anahtar Kelimeler

Kodlanmayan RNA, miRNA, mRNA

Kaynakça

• Kaikkonen MU,Lam MT,Glass CK. Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovasc Res. 2011;90:430-40.
• Güzelgül F. Orak hücreli anemilerde miRNA ekspresyon düzeylerinin RT-PCR ile belirlenmesi (Doktora tezi). Adana, Çukurova Üniversitesi, 2014.
• Güzelgül F. Aksoy K. Kodlanmayan RNA’ların işlevi ve tıpta kullanım alanları. Arşiv Kaynak Tarama Dergisi. 2009;18:141-55.
• Almeida MI,Reis RM,Calin GA. MicroRNA history: discovery, recent applications, and next frontiers. http://www.mirbase.org/index.shtml (Accessed: January 2015). Wei F, Yue F. MicroRNAs in neural cell development and brain diseases. Sci China Life Sci. 2011;54:1103-12.
• Bissels U, Bosio A, Wagner W. MicroRNAs are shaping the hematopoietic landscape. Haematologica. 2012;97:160-7.
• Großhans H. Regulation of microRNAs. Eds. New York, Springer Science Business Media, 2010.
• Treiber T, Treiber N, Meister G. Regulation of microRNA biogenesis and function. Tromb Haemotology. 2012;107:605-10.
• Curtis HJ, Sibley CR, Wood MJA. Mirtrons, an emerging class of atypical miRNA. Wiley Interdiscip Rev RNA. 2012; 3:617-32.
• Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004; 23:4051-60.
• Borchert GM,Lanier W,Davidson BL. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol.2006;13:1097-101.
• He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522-31.
• Ladewig E,Okamura K,Flynt AS, Westholm JO, Lai EC. Discovery of hundreds of mirtrons in mouse and human small RNA data. Genome Res.2012;22:1634-45.
• Hentze MW, Preiss T. Circular RNAs splicing’s enigma variations. EMBO J. 2013;32:923-5.Ledford H. Circular RNAs throw genetic for a loop. Nature. 2013;494:415.
• Gangaraju VK, Lin H. MicroRNAs: key regulators of stem cells. Nat Rev Mol Cell Biol. 2009;10:116-25.
• Zhao Y,Srivastava D. A developmental view of microRNA function. Trends Biochem Sci. 2007;32:189-97.
• Le MT,Xie H,Zhou B,Chia PH, Rizk P, Um M et al. MicroRNA-125b promotes neuronal differentiation in human cells by repressing multiple targets. Mol Cell Biol. 2009;29:5290- 305.Ambros V. MicroRNAs and developmental timing. Curr Opin Genet Dev.2011;21:511-17.
• Williams AE, Moschos SA, Perry MM, Barnes PJ, Lindsay MA. Maternally imprinted microRNAs are differentially expressed during mouse and human lung development. Dev Dyn. 2007;236: 572-80.
• Tunalı NE, Tiryakioğlu NO. Kanserde mikroRNA’ların rolü. Turkiye Klinikleri J Med Sci. 2010;30:1690-700.
• Saito Y,Liang G,Egger G,Friedman JM, Chuang JC, Coetzee GA et al. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell.2006;9:435-43.
• Das S, Ferlito M, Kent OA, Fox-Talbot K, Wang R, Liu D et al. Nuclear microRNA regulates the mitochondrial genome in the heart. Circ Res. 2012;110:1596-603.
• Li P, Jiao J, Gao G, Prabhakar BS. Control of mitochondrial activity by miRNAs. J Cell Biochem. 2012;113:1104-10.
• Sripada L, Tomar D, Singh R. Mitochondria: one of the destinations of miRNAs. Mitochondrion. 2012;12:593-99.
• Dorn GW II, MicroRNAs and butterfly effect. Cell cycle. 2013;12:707-8.
• Lee HC,Yang CW,Chen CY,Au LC. Single point mutation of microRNA may cause butterfly effect on alteration of global gene expression. Biochem Biophys Res Commun.2011;404:1065-69.
• Fiorucci G,Chiantore MV,Mangino G,Percario ZA, Affabris E, Romeo G. Cancer regulator microRNA: potential relevance in diagnosis, prognosis and treatment of cancer. Curr Med Chem. 2012;19:461-74.
• Xiao YF,Yong X,Fan YH, Lü MH, Yang SM, Hu CJ. MicroRNA detection in feces, sputum, pleural effusion and urine: novel tools for cancer screening.Oncol Rep.2013;30:535-44.
• Lässer C,O'Neil SE,Ekerljung L, Ekström K, Sjöstrand M, Lötvall J. RNA-containing exosomes in human nasal secretions. Am J Rhinol Allergy. 2011;25:89-93.
• Park NJ,Zhou H,Elashoff D,Henson BS, Kastratovic DA, Abemayor E et al. Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res. 2009;15:5473-77.
• Lawrie CH,Gal S,Dunlop HM,Pushkaran B,Liggins AP,Pulford K et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol.2008;141:672-75.
• Yousef M, Allmer J. miRNomics: MicroRNA Biology and Computational Analysis. New York, Humana Press, 2014.
• Kosaka N,Iguchi H,Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci.2010;101:2087-92.
• Calin GA, Dumitru CD,Shimizu M,Bichi R, Zupo S, Noch E et al. Frequent deletions and down- regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA.2002;99:15524-29.
• Weiler J,Hunziker J,Hall J. Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease? Gene Ther.2006;13:496-502.
• Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand 2 during cardiogenesis. Nature. 2005;436:214-20.
• Wienholds E,Kloosterman WP,Miska E. Alvarez-Saavedra E, Berezikov E, de Bruijn E et al. MicroRNA expression in zebrafish embryonic development. Science. 2005;309:310-1.
• Leidinger P,Backes C,Deutscher S, Schmitt K, Mueller SC, Frese Ket al. A blood based 12-miRNA signature of Alzheimer disease patients. Genome Biol.2013;14:78.
• Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE et al. Altered expression of microRNA in synovial fibroblast and synovial tissue in rheumatoid arthritis. Arthritis Rheum. 2008; 58:1001-09.
• Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M et al. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum. 2008;58:1284-92.
• Pauley KM, Satoh M, Chan AL, Bubb MR,Reeves WH, Chan EK. Upregulated miR-146a expression in peripheral blood mononuclear cell from rheumatoid arthritis patients. Arthritis Res Ther. 2008;10:101.
• van Rooij E,Purcell AL,Levin AA. Developing microRNA therapeutics. Circ Res.2012;110:496-507.
• Broderick JA, Zamore PD. MicroRNA therapeutics. Gene Therapy. 2011; 18:1104-10.
• Bissels U,Wild S,Tomiuk S,Hafner M, Scheel H, Mihailovic A et al. Combined characterization of microRNA and mRNA profiles delineates early differentiation pathways of CD133+ and CD34+ hematopoietic stem and progenitor cells. Stem Cells. 2011;5:847-57.
• Silahtaroglu A, Stenvang J. MicroRNAs epigenetic and disease. Essays Biochem. 2010;48:165- 85.
• Calin GA, Croce CM. MicroRNA signature in human cancers. Nat Rev Cancer. 2006;6:857-66.
• Correspondence Address / Yazışma Adresi