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RNAi RNA INTERFERENCE

Yıl 2017, Cilt: 6 Sayı: 1, 468 - 476, 01.01.2017

Öz

Backround/Aim: The identification of the sequence analysis of the genomes of many organisms has led to the emergence of a large number of genes whose functions are not yet known, and the search for the function of these genes has increased considerably. A genetic expression can be suppressed at different stages and information about the gene function can be obtained. Today, antisense strategies targeting the broad transcript are widely used to determine the function of specific genes. In the studies of the functions of the specific genes constructed using the antisense technique, translation of the transcript is inhibited using oligonucleotides conjugated to the corresponding genetic transcript. Studies using these techniques have led to the discovery of RNA interference RNAi . In this review, RNAi, current studies and benefits derived from these studies are discussed. Conclusion: RNA interference is an effective method for silencing/suppressing post-transcriptional gene expression. This mechanism is inherent in nature and has a wide range of applications in gene-protein function analysis in molecular biology, functional genomics research and gene therapy. Antisense-acting constructs are seen as an important milestone in molecular therapy in terms of silencing the target gene by suppressing complement mRNA, suppressing target gene expression, controlling gene expression, and thereby specifically targeting genes involved in disease mechanisms. Therefore, it is seen as a promising mechanism in the treatment of long, troublesome and failing diseases in the future.

Kaynakça

  • Akashi H, Miyagishi M, Taira K. Supression of gene expression by RNA interference in cultured plant cells. Antisense Nucleic Acid Drug Dev 2001, 11(6), 359-67.
  • Akashi H, Matsumoto S, Taira K. Gene discovery by ribozyme and siRNA libraries. Nature Reviews Molecular Cell Biology 2005, 6(5), 413-22.
  • Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular Biology of the Cell (5th edition), New York: Garland Science, 2008.
  • Alexander R, Krol VD, Lenting PE, Venestra J, Van Der Meer IM, Koes RE, Gerats AGM, Mol JNM, Stuitje AR. An anti-sense chalgone synthase gene in transgenic plants inhibits flower pigmentation. Nature 1988, 333, 866-869.
  • interference regulate expression of the small temporal RNAs that control C elegans developmental timing. Cell 2001, 6, 23-34.
  • Jorgensen RA, Cluster PD, English J, Que Q, Napoli CA. Chalcone synthase cosuppression phenotypes in petunia flowers: comparison of sense vs. antisense constructs and single-copy vs. complex T DNA sequences. Plant Mol Biol 1996, 31(5), 957-73.
  • Juliano RL, Dixit VR, Kang H, Kim TY, Miyamoto Y, Xu D. Epigenetic manipulation of gene expression: a toolkit for cell biologists. J Cell Biol 2005, 169, 847-857.
  • Karagüzel A, Kalay E, Celep F. RNA interferens (RNAi): gen sessizleştirilmesi ve tedavi edici uygulamaları. Uludağ Üniversitesi Tıp Fakültesi Dergisi 2007, 33(1), 41-44.
  • Keates AC, Fruehauf JH, Xiang S, Parker PD, Li CJ. Cequent Pharmaceuticals, Inc.:the biological pitcher for RNAi therapeutics. Pharmacogenomics 2007, 8, 867-871.
  • Kim DH, Rossi JJ. Strategies for silencing human disease using RNA interference. Nature Rev Gen 2007, 8, 173-84.
  • Kiriakidou M, Tan GS, Lamprinaki S, De Planel-Saguer M, Nelson PT, Mourelatos Z. An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell 2007, 129, 1141-1151.
  • Kortylewski M, Swiderski P, Herrmann A, Wang L, Kowolik C, Kujawski M, Lee H, Scuto A, Liu Y, Yang C, Deng J, Soifer HS, Raubitschek A, Forman S, Rossi JJ, Pardoll DM, Jove R, Yu H. In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses. Nature Biotech 2009, 27, 925-932.
  • Kruger K, Grabowski PJ, Zaug AJ, Sands J, Gottschling DE, Cech TR. Self- splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 1982, 31, 147-157.
  • Kumar P, Wu H, McBride JL, Jung KE, Kim MH, Davidson BL, Lee SK, Shankar P, Manjunath N. Transvascular delivery of small interfering RNA to the central nervous system. Nature 2007, 448(7149), 39-43.
  • Lares MR, Rossi JJ, Ouellet DL. RNAi and small interfering RNAs in human disease therapeutic applications. Trends Biotechnol 2010, 28, 570-579.
  • Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity tolin-14. Cell 1993, 75, 843-854.
  • Lee YS, Dutta A. MicroRNAs in cancer. Annu Rev Pathol Mech Dis 2009, 4, 199-227.
  • Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nature Cell Biol 2005, 7, 719-23.
  • MacDiarmid JA, Amaro-Mugridge NB, Madrid-Weiss J, Sedliarou I, Wetzel S, Kochar K, Brahmbhatt VN, Phillips L, Pattison ST, Petti C, Stillman B, Graham, RM, Brahmbhatt H. Sequential treatment of drug-resistant tumors with targeted minicells containing siRNA or a cytotoxic drug. Nature Biotech 2009, 27, 643-651.
  • Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 2004, 15, 185-197.
  • Mello CC, Conte D Jr. Revealing the world of RNA interference. Nature 2004, 431(7006), 338-42.
  • Mizuno T, Chou MY, Inouye M. A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA). Proc Natl Acad Sci USA 1984, 81, 1966-1970.
  • Morris KV, Rossi JJ. Lentiviral-mediated delivery of siRNAsfor antiviral therapy. Gene Ther 2006, 13, 553-8.
  • Napoli C, Lemieux C, Jorgensen R. Introduction of a chimeric chalcone synthase gene into Petunia result in supression of homologous revesible co-supression of homologous genes in trans. The Plant Cell 1990, 2, 279-289.
  • Nishida KM, Miyoshi K, Ogino A, Miyoshi T, Siomi H, Siomi MC. Roles of R2D2, a cytoplasmic D2 body component, in the endogenous siRNA pathway in Drosophila. Mol Cell 2013, 49(4), 680-91.
  • Plaisance-Bonstaff K, Renne R. Viral miRNAs. Methods Mol Biol 2011, 721, 43-66.
  • Portin P. The concept of the gene: short history and present status. Q Rev Biol 1993, 68, 173-223.
  • Rao DD, Vorhies JS, Senzer N, Nemunaitis J. siRNA vs. shRNA: Similarities and differences. Adv Drug Deliv Rev 2009, 61(9), 746-759.
  • Ruitz F, Vayssie L, Klotz C, Sperling L, Madeddu L. Homology-dependent gene silencing in Paramecium. Mol Biol Cell 1998, 9(4), 931-43.
  • Saenger W. Principles of Nucleic Acid Structure, New York: Springer- Verlag, 1984.
  • Sözbilir NB. Biyokimya. NB Sözbilir, N Bayşu(Ed.), Ankara: Güneş Tıp Kitabevi, 2008.
  • Stefani G, Slack FJ. Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol 2008, 9, 219-30.
  • Taylor J, Woodcock S. A perspective on the future of high-throughput RNAi screening: will CRISPR cut out the competition or can RNAi help guide the way? J Biomol Screen 2015, 20(8), 1040-51.
  • Veeramachaneni V, Makalowski W, Galdzicki M, Sood R, Makalowska I. Mammalian overlapping genes: the comparative perspective. Genome Res 2004, 14, 280-286.
  • Wies E, Mori Y, Hahn A, Kremmer E, Stürzl M, Fleckenstein B, Neipel F. The viral interferon-regulatory factor-3 is required for the survival of KSHV-infected primary effusion lymphoma cells. Blood 2008, 111(1), 320-7.
  • Yıldırım A, Bardakçı F, Karataş M, Tanyolaç B. Moleküler Biyoloji, A. Yıldırım(Ed.), Ankara: Nobel Yayın Dağıtım, 2010.
  • Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 2003, 17(24), 3011-6.
  • Zamecnik PC, Stephanson ML. Inhibition of Raus sarcoma virus replication and cell transformation by a spesific oligodeoxynucleotide. Proc Natl Acad Sci USA 1978, 75, 280-4.
  • Zamore PD, Tuschl T, Sharp PA, Bartel DP. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 2000, 101(1), 25-33.

RNA Interferens RNAi

Yıl 2017, Cilt: 6 Sayı: 1, 468 - 476, 01.01.2017

Öz

Özbilgi/Amaç: Birçok organizmanın genomunun dizi analizlerinin belirlenmesi ile fonksiyonu henüz bilinmeyen çok sayıda gen açığa çıktığı için bu genlerin fonksiyonlarının araştırıldığı çalışmaların sayısı artmıştır. Bir genin ifadesi farklı aşamalarda baskılanarak hedef genin fonksiyonuyla ilgili bilgi edinilebilir. Günümüzde genin transkriptini hedef alan antisense stratejileri özgül genlerin fonksiyonunun belirlenmesinde yaygın bir şekilde kullanılmaktadır. Antisense tekniği kullanılarak yapılan özgül genlerin fonksiyonlarının belirlenmesini amaçlayan çalışmalarda ilgili genin transkriptine eşlenik oligonükleotidler kullanılarak transkriptin translasyonu engellenmektedir. Bu teknikler kullanılarak yapılan çalışmalar RNA interferensin RNAi keşfedilmesine yol açmıştır. Bu derlemede RNAi, mevcut çalışmalar ve bu çalışmalar doğrultusunda sağlanan faydalar konu edilmiştir. Sonuç: RNA interferens, transkripsiyon sonrası gen ekspresyonunun susturulması/baskılanması için etkili bir metottur. RNA interferens mekanizması doğada var olan bir mekanizma olup, aynı zamanda moleküler biyolojide gen-protein işlevi analizinde, fonksiyonel genomik araştırmalarda ve gen tedavisinde geniş bir uygulama alanına sahiptir. Antisens etki gösteren yapılar, komplementer mRNA’yı degrade ederek ya da translasyonu baskılayarak hedef geni susturarak ilgili gen ifadesinin engellenmesi mekanizmasıyla etki ederler. Bu mekanizmadan yola çıkılarak hastalıkların patogenezisinde rol oynayan genlerin ekspresyonunun kontrolü ile moleküler temelli özgün tedavi yöntemlerinin geliştirilmesi ön görülmektedir. Sonuç olarak bu mekanizmayı içeren yöntemler çoğu zaman başarısızlıkla sonlanan, tedavi süreci uzun ve etkilenen bireyler açısından yıpratıcı olan hastalıkların tedavisinde umut vaat edicidir.

Kaynakça

  • Akashi H, Miyagishi M, Taira K. Supression of gene expression by RNA interference in cultured plant cells. Antisense Nucleic Acid Drug Dev 2001, 11(6), 359-67.
  • Akashi H, Matsumoto S, Taira K. Gene discovery by ribozyme and siRNA libraries. Nature Reviews Molecular Cell Biology 2005, 6(5), 413-22.
  • Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular Biology of the Cell (5th edition), New York: Garland Science, 2008.
  • Alexander R, Krol VD, Lenting PE, Venestra J, Van Der Meer IM, Koes RE, Gerats AGM, Mol JNM, Stuitje AR. An anti-sense chalgone synthase gene in transgenic plants inhibits flower pigmentation. Nature 1988, 333, 866-869.
  • interference regulate expression of the small temporal RNAs that control C elegans developmental timing. Cell 2001, 6, 23-34.
  • Jorgensen RA, Cluster PD, English J, Que Q, Napoli CA. Chalcone synthase cosuppression phenotypes in petunia flowers: comparison of sense vs. antisense constructs and single-copy vs. complex T DNA sequences. Plant Mol Biol 1996, 31(5), 957-73.
  • Juliano RL, Dixit VR, Kang H, Kim TY, Miyamoto Y, Xu D. Epigenetic manipulation of gene expression: a toolkit for cell biologists. J Cell Biol 2005, 169, 847-857.
  • Karagüzel A, Kalay E, Celep F. RNA interferens (RNAi): gen sessizleştirilmesi ve tedavi edici uygulamaları. Uludağ Üniversitesi Tıp Fakültesi Dergisi 2007, 33(1), 41-44.
  • Keates AC, Fruehauf JH, Xiang S, Parker PD, Li CJ. Cequent Pharmaceuticals, Inc.:the biological pitcher for RNAi therapeutics. Pharmacogenomics 2007, 8, 867-871.
  • Kim DH, Rossi JJ. Strategies for silencing human disease using RNA interference. Nature Rev Gen 2007, 8, 173-84.
  • Kiriakidou M, Tan GS, Lamprinaki S, De Planel-Saguer M, Nelson PT, Mourelatos Z. An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell 2007, 129, 1141-1151.
  • Kortylewski M, Swiderski P, Herrmann A, Wang L, Kowolik C, Kujawski M, Lee H, Scuto A, Liu Y, Yang C, Deng J, Soifer HS, Raubitschek A, Forman S, Rossi JJ, Pardoll DM, Jove R, Yu H. In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses. Nature Biotech 2009, 27, 925-932.
  • Kruger K, Grabowski PJ, Zaug AJ, Sands J, Gottschling DE, Cech TR. Self- splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 1982, 31, 147-157.
  • Kumar P, Wu H, McBride JL, Jung KE, Kim MH, Davidson BL, Lee SK, Shankar P, Manjunath N. Transvascular delivery of small interfering RNA to the central nervous system. Nature 2007, 448(7149), 39-43.
  • Lares MR, Rossi JJ, Ouellet DL. RNAi and small interfering RNAs in human disease therapeutic applications. Trends Biotechnol 2010, 28, 570-579.
  • Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity tolin-14. Cell 1993, 75, 843-854.
  • Lee YS, Dutta A. MicroRNAs in cancer. Annu Rev Pathol Mech Dis 2009, 4, 199-227.
  • Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nature Cell Biol 2005, 7, 719-23.
  • MacDiarmid JA, Amaro-Mugridge NB, Madrid-Weiss J, Sedliarou I, Wetzel S, Kochar K, Brahmbhatt VN, Phillips L, Pattison ST, Petti C, Stillman B, Graham, RM, Brahmbhatt H. Sequential treatment of drug-resistant tumors with targeted minicells containing siRNA or a cytotoxic drug. Nature Biotech 2009, 27, 643-651.
  • Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 2004, 15, 185-197.
  • Mello CC, Conte D Jr. Revealing the world of RNA interference. Nature 2004, 431(7006), 338-42.
  • Mizuno T, Chou MY, Inouye M. A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA). Proc Natl Acad Sci USA 1984, 81, 1966-1970.
  • Morris KV, Rossi JJ. Lentiviral-mediated delivery of siRNAsfor antiviral therapy. Gene Ther 2006, 13, 553-8.
  • Napoli C, Lemieux C, Jorgensen R. Introduction of a chimeric chalcone synthase gene into Petunia result in supression of homologous revesible co-supression of homologous genes in trans. The Plant Cell 1990, 2, 279-289.
  • Nishida KM, Miyoshi K, Ogino A, Miyoshi T, Siomi H, Siomi MC. Roles of R2D2, a cytoplasmic D2 body component, in the endogenous siRNA pathway in Drosophila. Mol Cell 2013, 49(4), 680-91.
  • Plaisance-Bonstaff K, Renne R. Viral miRNAs. Methods Mol Biol 2011, 721, 43-66.
  • Portin P. The concept of the gene: short history and present status. Q Rev Biol 1993, 68, 173-223.
  • Rao DD, Vorhies JS, Senzer N, Nemunaitis J. siRNA vs. shRNA: Similarities and differences. Adv Drug Deliv Rev 2009, 61(9), 746-759.
  • Ruitz F, Vayssie L, Klotz C, Sperling L, Madeddu L. Homology-dependent gene silencing in Paramecium. Mol Biol Cell 1998, 9(4), 931-43.
  • Saenger W. Principles of Nucleic Acid Structure, New York: Springer- Verlag, 1984.
  • Sözbilir NB. Biyokimya. NB Sözbilir, N Bayşu(Ed.), Ankara: Güneş Tıp Kitabevi, 2008.
  • Stefani G, Slack FJ. Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol 2008, 9, 219-30.
  • Taylor J, Woodcock S. A perspective on the future of high-throughput RNAi screening: will CRISPR cut out the competition or can RNAi help guide the way? J Biomol Screen 2015, 20(8), 1040-51.
  • Veeramachaneni V, Makalowski W, Galdzicki M, Sood R, Makalowska I. Mammalian overlapping genes: the comparative perspective. Genome Res 2004, 14, 280-286.
  • Wies E, Mori Y, Hahn A, Kremmer E, Stürzl M, Fleckenstein B, Neipel F. The viral interferon-regulatory factor-3 is required for the survival of KSHV-infected primary effusion lymphoma cells. Blood 2008, 111(1), 320-7.
  • Yıldırım A, Bardakçı F, Karataş M, Tanyolaç B. Moleküler Biyoloji, A. Yıldırım(Ed.), Ankara: Nobel Yayın Dağıtım, 2010.
  • Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 2003, 17(24), 3011-6.
  • Zamecnik PC, Stephanson ML. Inhibition of Raus sarcoma virus replication and cell transformation by a spesific oligodeoxynucleotide. Proc Natl Acad Sci USA 1978, 75, 280-4.
  • Zamore PD, Tuschl T, Sharp PA, Bartel DP. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 2000, 101(1), 25-33.
Toplam 39 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Research Article
Yazarlar

Ayşe Nur Akkoç Bu kişi benim

Nihat Toplu Bu kişi benim

Yayımlanma Tarihi 1 Ocak 2017
Yayımlandığı Sayı Yıl 2017 Cilt: 6 Sayı: 1

Kaynak Göster

APA Akkoç, A. N., & Toplu, N. (2017). RNA Interferens RNAi. Animal Health Production and Hygiene, 6(1), 468-476.