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.