Human Cytomegalovirus-encoded microRNA regulates expression of multiple genes involved in replication
Our ability to understand the biology of viruses depends not only on functional analysis of genes they encode but also on specific regulation of those genes during viral infection. In herpesviruses, virus gene regulation is highly complex and plays a significant role in determining the virus replication cycle during acute, latent, or persistent infection. The discovery that many herpesviruses express small regulatory RNAs, known as microRNAs (miRNAs), has opened up a whole new area of research in regulation of gene expression. A recent paper demonstrates that a microRNA expressed by human cytomegalovirus is able to regulate multiple virus genes, including one gene thought to be crucial for both acute and latent stages of viral infection in the host. Expression of this microRNA results in a significant reduction in viral replication. This work therefore demonstrates that viral microRNAs can regulate multiple viral genes and can have significant effects on the replication of a virus.
Although multiple studies have documented the expression of over 70 novel virus-encoded miRNAs, the targets and functions of most of these regulatory RNA species are unknown. In this study a comparative bioinformatics approach was employed to identify potential human cytomegalovirus (HCMV) mRNA targets of a virus-encoded miRNA. Bioinformatics analysis of the known HCMV mRNA 3 untranslated regions revealed 14 potential virus transcripts that were predicted to contain functional target sites for the miRNA. Three of the 14 HCMV miRNA targets were validated, including the major immediate early gene encoding IE72. Further analysis of IE72 regulation by the miRNA with clones encoding the complete major immediate early region revealed that the IE72 3 UTR target site is necessary and sufficient to direct miRNA-specific inhibition of expression in transfected cells. In addition, miRNA regulation is mediated through translational inhibition rather than RNA degradation. Premature expression of the miRNA during HCMV infection resulted in a significant decrease in genomic viral DNA levels, suggesting a functional role in regulating the expression of genes involved in virus replication.
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Tags: Biology, Genetics, Microbiology, Science, Virology
“A percent paper demonstrates…” Damn those percent…! And spellcheckers. “Recent” might be better?
Thank you Edward. :-)