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RNA干渉 RNAi (interference) - 埼玉大学RNA干扰(RNA干扰)-埼玉大学干渉.ppt
* * Silencing triggers in the form of double-stranded RNA may be presented in the cell as synthetic RNAs, replicating viruses or may be transcribed from nuclear genes. These are recognized and processed into small interfering RNAs by Dicer. The duplex siRNAs are passed to RISC (RNA-induced silencing complex), and the complex becomes activated by unwinding of the duplex. Activated RISC complexes can regulate gene expression at many levels. Almost certainly, such complexes act by promoting RNA degradation and translational inhibition. However, similar complexes probably also target chromatin remodelling. Amplification of the silencing signal in plants may be accomplished by siRNAs priming RNA-directed RNA polymerase (RdRP)-dependent synthesis of new dsRNA. This could be accomplished by RISC-mediated delivery of an RdRP or by incorporation of the siRNA into a distinct, RdRP-containing complex. * * Fig. 1. The biogenesis and function of endogenous small RNAs in animals, and in plants and fungi. (A) In animals, microRNA (MIR) genes (top) are transcribed by Pol II into microRNA (miRNA) precursors, which are processed by DROSHA and DICER (DICER1) into miRNAs. The miRNAs are bound by an effector protein Argonaute (AGO) and cause the cleavage or translational inhibition of target mRNAs. In animals, despite the fact that each miRNA is able to regulate scores of target transcripts, genetic studies show that one major target underlies the role of a miRNA in a developmental process. Related miRNAs (light and dark blue) often have shared predicted targets, but genetic studies reveal that members of a miRNA family may have distinct developmental functions. (B) Endogenous siRNAs in S. pombe and in plants are generated from long transcripts from repeated DNA or transposons via the activities of RNA-dependent RNA polymerases (RdRP) and Dicer. Histone H3 lysine 9 (H3-K9) methylation and the siRNAs complexed with AGO act in a self-reinforcing loop to maintain heterochromatin at the lo
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