Processing of virus-derived cytoplasmic primary-microRNAs

MicoRNAs (miRNAs) are small noncoding RNAs that associate with Argonaute (AGO) family member proteins to mediate silencing of host mRNA transcripts. A number of DNA viruses and a single retrovirus exploit this pathway to generate their own miRNAs in an effort to self regulate or combat the host immune response to infection. While natural examples of viral miRNAs have been limited to nuclear viruses, manipulation of cytoplasmic-restricted RNA virus genomes revealed the ability of these vectors to produce abundant levels of mature, functional miRNAs, exclusively within the cytoplasm. This novel processing mechanism is found to be dependent upon the ribonuclease (RNAse) III proteins Drosha and Dicer, while processing is able to proceed in the absence of the canonical dsRNA binding proteins DiGeorge syndrome critical region gene 8 (DGCR8), Tar RNA binding protein 2 (TRBP2), and protein kinase R activating protein (PACT). Processing of cytoplasmic restricted primary-miRNA transcripts (c-pri-miRNAs) corresponds with virus-induced redistribution of Drosha, implicating the formation of a noncanonical microprocessor. This review will discuss c-pri-miRNA processing, the mechanism of miRNA production, and the implications of a virus-induced cytoplasmic microprocessor.