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The pre-miRNA is cleaved in the cytoplasm to create a microRNA duplex (miRNA:miRNA*, passenger strand designated with asterisk) containing the mature miRNA. The miRNA gene is transcribed to generate a primary microRNA (pri-miRNA) precursor molecule that undergoes nuclear cleavage to form a precursor microRNA (pre-miRNA). The level of complementarity between the guide and mRNA target determines which silencing mechanism will be employed cleavage of target messenger RNA (mRNA) with subsequent degradation or translation inhibition Fig. The miRNA functions as a guide by base-pairing with target mRNA to negatively regulate its expression. Mature miRNA is generated through two-step cleavage of primary miRNA (pri-miRNA), which incorporates into the effector complex RNA-induced silencing complex (RISC). MiRNA are small, evolutionary conserved, single-stranded, non-coding RNA molecules that bind target mRNA to prevent protein production by one of two distinct mechanisms. Although little is currently known about the specific targets and biological functions of miRNA molecules thus far, it is evident that miRNA plays a crucial role in the regulation of gene expression controlling diverse cellular and metabolic pathways. To date, 940 distinct miRNAs molecules have been identified within the human genome ( accessed July 20, 2010). It is predicted that miRNA account for 1-5% of the human genome and regulate at least 30% of protein-coding genes. MicroRNA (miRNA), originally discovered in Caenorhabditis elegans, is found in most eukaryotes, including humans. Detailed knowledge of the microRNA pathways is essential for understanding their physiological role and the implications associated with dysfunction and dysregulation. The P-body model outlines microRNA sorting and shuttling between specialized P-body compartments that house enzymes required for slicer –dependent and –independent silencing, addressing the reversibility of these silencing mechanisms. Recent evidence indicates that P-bodies are essential for microRNA-mediated gene silencing and that RISC assembly and silencing occurs primarily within P-bodies.
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The degree and nature of the complementarity between the microRNA and target determine the gene silencing mechanism, slicer-dependent mRNA degradation or slicer-independent translation inhibition. Various RISC assembly models have been proposed and research continues to explore the mechanism(s) of RISC loading and activation. MicroRNA assembles into RISC, activating the complex to target messenger RNA (mRNA) specified by the microRNA. The regulatory functions of microRNAs are accomplished through the RNA-induced silencing complex (RISC). How microRNA precursors are sorted to the different pathways is unclear but appears to be determined by the site of origin of the microRNA, its sequence and thermodynamic stability. However, alternative biogenesis pathways exist that differ in the number of cleavage events and enzymes responsible. The conventional biogenesis pathway consists of two cleavage events, one nuclear and one cytoplasmic.
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MicroRNAs are transcribed by RNA polymerases II and III, generating precursors that undergo a series of cleavage events to form mature microRNA. MicroRNAs are small, highly conserved non-coding RNA molecules involved in the regulation of gene expression.