Dynamic Protein-RNA recognition in primary MicroRNA processing

MicroRNAs are prevalent regulators of gene expression, controlling most of the proteome in multicellular organisms. To generate the functional small RNAs, precise processing steps are required. In animals, microRNA biogenesis is initiated by Microprocessor that minimally consists of the Drosha enzyme and its partner, DGCR8. This first step is critical for selecting primary microRNAs, and many RNA-binding proteins and regulatory pathways target both the accuracy and efficiency of microRNA maturation. Structures of Drosha and DGCR8 in complex with primary microRNAs elucidate how RNA structural features rather than sequence provide the framework for substrate recognition. Comparing multiple states of Microprocessor and the closely related Dicer homologs shed light on the dynamic protein-RNA complex assembly and disassembly required to recognize RNAs with diverse sequences via common structural features.