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RNA İNTERFERANS (RNAİ)

RNA interferans, uygun çift zincirli RNA’nın hücreye girdiği zaman, endojenik komplementer mRNA dizisinin parçalanmasına yol açan, transkripsiyon sonrası gen susturma mekanizmasıdır. RNA interferans, Dicer adı verilen bir RNase III enzimi tarafından çift zincirli RNA’nın küçük engelleyici RNA’lara (siRNA) kesilmesi ile başlamaktadır. Bu siRNA’lar daha sonra, bir multiprotein-RNA nükleaz kompleksi olan, RNA- indükleyici baskılama kompleksine (RISC) bağlanır. RISC, siRNA’ları komplementer mRNA’yı bulmak için kullanır ve hedef mRNA’yı endonükleolitik olarak keser. Neticede spesifik mRNA’nın azalması uygun protein(ler)in azalmasına yol açar. RNA interferans ve RNA baskılamanın diğer formları olan transkripsiyon sonrası gen baskılama/co-supresyon ve quelling bitkiler, hayvanlar, fungus ve protozoa gibi geniş bir organizma çeşidinde gözlenmiştir. RNA interferans doğal bir mekanizma olmakla birlikte in vitro olarak sentezlenen siRNA’lar kullanılarak endojenik genlerin ekspresyonu baskılanabilmektedir. Bu yüzden RNA interferans moleküler biyolojide gen fonksiyonu analizinde ve aynı zamanda gen terapisinde geniş bir uygulama alanına sahiptir. Bu derlemede RNA interferans ve onun spesifik varyantları olan transkripsiyon sonrası gen baskılama/co-supresyon ve quelling’den, RNA interferansın mekanizmasından ve onun tedavi alanındaki uygulamalarından bahsedilmektedir.

Anahtar Kelimeler:

RNA İnterferans, RNAi, siRNA, Gen baskılama

RNA INTERFERENCE (RNAi)

RNA interference is a post-transcriptional gene silencing process during which endogenous complementary messenger RNA is destroyed upon introduction of the corresponding double-stranded RNA into the cell. The initation of RNA interference occurs with the processing of double-stranded RNA into small interfering RNAs (siRNAs), by an RNase III enzyme called Dicer. These siRNAs are then incorporated into the RNA-Induced Silencing Complex (RISC), a multiprotein-RNA nuclease complex. RISC uses these siRNAs to find complementary mRNA and endonucleolytically cleave target mRNA. Consequently, the reduction of specific mRNAs leads to the reduction of the corresponding protein(s). RNA interference and other forms of RNA silencing such as posttranscriptional gene silencing/co-suppression, quelling have been observed in a wide variety of organisms such as plants, animals, fungi, and protozoa. Although RNA interference is a natural phenomenon, it can be used to silence expression of endogenous genes using in vitro synthesized siRNAs. Therefore, RNA interference is promptly utilized as a gene function analysis tool in molecular biology and also in gene therapy. This review describes RNA interference and its specific variants, post-transcriptional gene silencing/co-suppression and quelling, mechanism of RNA interference and applications of RNA interference as therapeutic.

Keywords:

RNA İnterferans, RNAi, siRNA, Gen baskılama,

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