MicroRNAs found for the first time in a retrovirus

MicroRNAs (miRNAs) are small non-coding RNAs that play a regulatory role in many cellular processes such as immune function, apoptosis and tumorigenesis. MicroRNAs are about 22 nucleotide long (on average) and they typically derive from primary transcripts "snipped" during a process called "endonucleolytic cleavage," which involves a protein that recognizes a double-helix RNA and cleaves the nucleotides in halves for degradation. MicroRNAs are post-transcriptional regulators, meaning they regulate what genes get transcripted by binding to their complementary RNA transcripts and thus preventing them to produce proteins.

Most eukaryotes, as well as many viruses, encode miRNAs. As you know, there are two kinds of viruses, depending on whether they carry DNA or RNA, and until now miRNAs had been found in DNA viruses only.

"Although limited studies exist, a preliminary model suggests that DNA viruses will use miRNAs for varied activities, including: regulation of latent/persistent infection, evasion of the innate and adaptive immune responses, and promotion of cell viability [1]."

A new study published in last week's issue of PNAS [1] reports the finding of miRNA in a retrovirus, namely the bovine leukemia virus (BLV), a virus that is associated with B-cell tumors both in cattle and sheep. How the virus initiates these tumors remains a mystery.

"Essentially all tumor cells are positive for the viral genome; however, very little, if any, viral mRNAs and proteins are detected in most cells [1]."

The finding that BLV encodes miRNAs is quite surprising because the general thought was that it would be deleterious for a retrovirus to encode miRNA, since it would have to come from the cleavage process I described above, and this could potentially affect the viral genome. In their study, Kincaid et al. identify a cluster of five miRNAs expressed from the BLV genome and also describe the mechanism by which these transcripts escape cleavage. Interestingly, one of the five miRNAs is functional and identical to the target portion in the host. The researchers demonstrate that the two miRNAs, the viral one and the host's, target transcripts that have been previously associated with B-cell cancerogenesis in mice, thus shedding new light on how the virus could initiate the cancer in the host.

"In summary, we demonstrate that an RNA virus expresses abundant, evolutionarily conserved miRNAs, including at least one that functions as an analog to a host oncogenic miRNA. These findings open up a role for noncoding RNAs in retroviral-associated tumorigenesis, and suggest the possibility that other retro- viruses exist that use noncoding RNAs in their infectious cycles."

Kincaid, R., Burke, J., & Sullivan, C. (2012). From the Cover: RNA virus microRNA that mimics a B-cell oncomiR Proceedings of the National Academy of Sciences, 109 (8), 3077-3082 DOI: 10.1073/pnas.1116107109