title: Cellular functions of the microprocessor.
abstract: The microprocessor is a complex comprising the RNase III enzyme Drosha and the double-stranded RNA-binding protein DGCR8 (DiGeorge syndrome critical region 8 gene) that catalyses the nuclear step of miRNA (microRNA) biogenesis. DGCR8 recognizes the RNA substrate, whereas Drosha functions as an endonuclease. Recent global analyses of microprocessor and Dicer proteins have suggested novel functions for these components independent of their role in miRNA biogenesis. A HITS-CLIP (high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation) experiment designed to identify novel substrates of the microprocessor revealed that this complex binds and regulates a large variety of cellular RNAs. The microprocessor-mediated cleavage of several classes of RNAs not only regulates transcript levels, but also modulates alternative splicing events, independently of miRNA function. Importantly, DGCR8 can also associate with other nucleases, suggesting the existence of alternative DGCR8 complexes that may regulate the fate of a subset of cellular RNAs. The aim of the present review is to provide an overview of the diverse functional roles of the microprocessor.
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Macias
authors.forename: Ross A
authors.initials: RA
authors.lastname: Cordiner
authors.forename: Javier F
authors.initials: JF
authors.lastname: Cáceres
mesh_terms: D004062:DiGeorge Syndrome / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D011506:Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins; D043244:Ribonuclease III / Q000378:metabolism*
chemical_list: C474043:DGCR8 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; C517918:DROSHA protein, human; D043244:Ribonuclease III