miRNA biogenesis overview.

<p>The majority of host and viral miRNAs begin as longer RNAs (pri-miRNAs) transcribed by host RNA Pol II that are recognized and processed by the host Microprocessor complex to produce a short stem-loop RNA (pre-miRNA). However, a minority of viruses utilize noncanonical mechanisms in the biogenesis of pre-miRNA molecules. Herpesvirus saimiri (HVS) encodes Sm class U RNAs (HSURs) that are transcribed by RNA Pol II and subsequently processed by the host Integrator complex to generate pre-miRNAs <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003018#ppat.1003018-Cazalla1" target="_blank">[115]</a>. The miRNAs encoded by mouse gammaherpesvirus 68 (MHV68) and BLV are both transcribed by host RNA Pol III <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003018#ppat.1003018-Pfeffer1" target="_blank">[35]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003018#ppat.1003018-Kincaid1" target="_blank">[39]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003018#ppat.1003018-Bogerd1" target="_blank">[116]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003018#ppat.1003018-Diebel1" target="_blank">[117]</a>. The MHV68 miRNAs are processed from larger tRNA-like RNAs by host tRNase Z and possibly additional factors to generate pre-miRNAs. Pre-miRNAs are exported to the cytoplasm where they are cleaved into short ∼22 nt duplex RNAs by the host enzyme Dicer. One strand of the duplex may be incorporated into an Argonaute protein containing effector complex known as RISC. The incorporated miRNA directs RISC to target RNAs. Most commonly for animal host and virus-encoded miRNAs, imperfectly complementary base pairing occurs between miRNA and mRNA target resulting in translation inhibition and mRNA turnover. However rarely, perfect base pairing can occur resulting in siRNA-like RNA cleavage and has been reported for polyomaviruses and some herpesviruses.