Biogenesis of micro (mi) and silencing (si)RNAs Biogenesis of micro (mi) and silencing (si)RNAs. (Left) miRNA encoding genes are transcribed by RNA pol II into a primary miRNA (pri-miRNA), which is 5′-capped and polyadenylated as is typical of mRNA coding primary transcripts. This pri-miRNA is subjected to processing within the nucleus by the action of the Drosha-DGCR8 nuclease, which trims sequences from both 5′ and 3′ ends to generate the pre-miRNA. This partially processed double-stranded RNA is transported through the nuclear pore by exportin-5. The cytoplasmic pre-miRNA is then trimmed further by the action of the heterodimeric nuclease termed Dicer (TRBP-Dicer), to form the 21-22 nt miRNA duplex. One of the two resulting 21–22 nucleotide-long RNA strands is selected, the duplex unwound, and the selected strand loaded into the RNA induced silencing complex, or RISC complex thereby generating the mature, functional miRNA. Following target mRNA location and sequence-specific miRNA-mRNA annealing, the functional miRNA can modulate mRNA function by one of three mechanisms: translational repression, mRNA destabilization by mRNA deadenylation, or mRNA degradation. (Right) The siRNA pathway generates functional siRNAs from large double stranded RNAs that are formed either intracellularly by RNA-RNA hybridization (inter- or intramolecular) or from extracellular sources such as RNA viruses. These viral dsRNAs are again processed to ~22 nt siRNA dsRNA segments via the heterodimeric Dicer nuclease, loaded into the Ago2-containing RISC complex, one strand is then selected to generate the siRNA that locates target RNA sequences via sequence-specific siRNA-RNA annealing. This ternary target RNA-siRNA-Ago2 complex induces RNA cleavage, which inactivates the target RNA. Source: RNA Synthesis, Processing, & Modification, Harper's Illustrated Biochemistry, 30e Citation: Rodwell VW, Bender DA, Botham KM, Kennelly PJ, Weil P. Harper's Illustrated Biochemistry, 30e; 2015 Available at: https://accessmedicine.mhmedical.com/DownloadImage.aspx?image=/data/books/1366/rod_ch36_f017.png&sec=73245250&BookID=1366&ChapterSecID=73245151&imagename= Accessed: October 21, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved