How human Microprocessor recognizes primary microRNAs and finds the correct cleavage sites

Microprocessor is an RNase III enzyme complex that recognizes long RNA stem-loop structures and cleaves doublestranded RNAs. It is comprised of a catalytic subunit DROSHA and a dimeric RNA-binding cofactor DGCR8 (DiGeorge Syndrome Critical Region 8). The most pronounced function of the protein complex is to process primary microRNAs (pri-miRNAs) in nucleus for initiating microRNA biogenesis. Since this step plays a critical role in determining the miRNA seed sequence that base-pairs with its target mRNAs for silencing, the cleavage sites on pri-miRNAs must be precisely selected. Microprocessor recognizes several pri-miRNA features, including double-stranded RNA−single-stranded RNA junctions, for determining the substrate binding orientation and finding the correct cleavage sites. Structural studies on a number of RNase III proteins have shown various mechanisms used for the precise selection of the cleavage sites, which are useful to understand those involved in Microprocessor. Recent biochemical and systematic mutational studies on human Microprocessor provide deep insights into the processing mechanisms and open up many interesting questions to be addressed by future structural studies.