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RNA interference and human disease
Author/Authors :
Cheng، Jerry C. نويسنده , , Moore، Theodore B. نويسنده , , Sakamoto، Kathleen M. نويسنده ,
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روزنامه با شماره پیاپی سال 2003
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The completion of the human genome project has left researchers searching for an efficient method to study gene function in mammalian cells. RNA interference (RNAi) is an evolutionarily conserved post-transcriptional gene silencing (PTGS) mechanism mediated by double-stranded RNA (dsRNA).The dsRNA is processed into small duplex RNA molecules of approximately 21-22 nucleotides (nts) termed small interfering RNAs (siRNAs) by a RNase III enzyme called Dicer. Interaction of siRNAs with a multi-protein complex, termed the RNA-induced silencing complex (RISC), results in sequence specific association of the activated RISC complex with the cognate RNA transcript (Fig. 1). This interaction leads to sequence-specific cleavage of the target transcript. Originally discovered in Caenorhabditis elegans, the study of RNAi in mammalian cells has blossomed in the last couple of years with the discovery that introduction of siRNA molecules directly into somatic mammalian cells circumvents the non-specific response vertebrate cells have against larger dsRNA molecules. Emerging as a powerful tool for reverse genetic analysis, RNAi is rapidly being applied to study the function of many genes associated with human disease, in particular those associated with oncogenesis and infectious disease. This review summarizes the mechanism of RNAi and provides an overview of its current applications in medicine.
Keywords :
Adrenal , Adrenal cortex , Development, steroidogenic axis , Hypothalamic-pituitary-adrenal/gonadal axis , Nuclear receptor, NR0B1 , Steroidogenic factor 1 , DAX1, adrenal hypoplasia congenital
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