Computational Biology and Chemistry 31 (2007) 124–126 Brief communication HBV-encoded microRNA candidate and its target Wei-Bo Jin a,b , Fang-Li Wu a , Dong Kong a , Ai-Guang Guo a,b,∗ a College of Life Science, Northwest A&F University, Yangling, Shaanxi 712100, China b Key Laboratory of Agriculture Molecular Biology in Shaanxi, Yangling, Shaanxi 712100, China Received 24 October 2006; received in revised form 18 January 2007; accepted 21 January 2007 Abstract MicroRNAs (miRNAs) are a group of short (∼22 nt) noncoding RNAs that specifically regulate cellular gene expression at the post-transcriptional level. miRNA precursors (pre-miRNAs), which are imperfect stem loop structures of ∼70 nt, are processed into mature miRNAs by cellular RNases III. To date, hundreds of miRNAs and their corresponding targets have been reported in kinds of species. Although only a few of these miRNA/target pairs have been functionally verified, some do play important roles in regulating normal development and physiology. Several viruses (e.g. the Epstein-Barr virus and human herpesvirus Kaposi’s sarcoma-associated herpesvirus) has been reported to encode miRNAs. Here, we extend the analysis of miRNA-encoding potential to the Hepatitis B virus (HBV). Using computational approaches, we found that HBV putatively encodes only one candidate pre-miRNA. We then matched deduced mature miRNA sequence from this pre-miRNA against a database of 3 ′ untranslated sequences (UTR) from the human genome. Surprisingly, none of cellular transcripts could potentially be targeted by the viral miRNA (vmiRNA) sequence. However, one viral mRNA was found to be targeted by the vmiRNA when we searched the target from viral mRNAs. We propose that HBV has evolved to use vmiRNAs as a means to regulate its own gene expression for its benefit. © 2007 Elsevier Ltd. All rights reserved. Keywords: HBV; MicroRNA; Identification; Target The first miRNA to be discovered was the Caenorhabditis elegans heterochronic gene lin-4, which inhibits translation by pairing with partially homologous sequences lin-14 in the 3 ′ untranslated region (UTR) (Lee et al., 1993; Fire et al., 1998; Hunter and Poethig, 2003). To date, thousands of miRNAs have been found in animals, plants and virus (Griffiths-Jones, 2004). Structurally, microRNAs (miRNAs) are 19–25 nucleotide RNAs processed from short stem-loop precursors that can be encoded in genomes of plants, animals and viruses. According to the current understanding, miRNA is firstly transcribed as long primary miRNA, which is processed into 60–70 nt miRNA precursor (pre-miRNA) by nuclear RNase III Drosha (Lee et al., 2002, 2003). Then the pre-miRNA is transported from nucleus to cytoplasm by Exportin-5 (Kim, 2004; Zeng and Cullen, 2004) and further cleaved into ∼22 nt duplexes (Bartel, 2004). Although the exact mechanism by which miRNA regulates gene expression is not completely understood, several experi- ∗ Corresponding author at: College of Life Science, Northwest A&F Univer- sity, Yangling, Shaanxi 712100, China. Tel.: +86 29 8702 6171; fax: +86 29 8709 2262. E-mail address: guoaiguang@yahoo.com.cn (A.-G. Guo). mental observations have been made to generalize the rules of miRNA-target binding. The most important one among them is the base 2–8 of the 5 ′ end of the miRNA (named as seed sequence) must perfectly complement with the 3 ′ UTR of tar- get mRNA. Other general features like optimum minimum free energy (MFE) of the miRNA:mRNA complex also benefit the function of miRNAs. Recently, researchers are more and more interested in the interaction of miRNA and virus mRNA. Pfeffer et al. (2004) identified virus-encoded miRNA sequences in Epstein-Barr virus (EBV) infected cells. They reported that EBV encodes five miRNAs which are capable of regulating the expression of viral genes involved in latency and modulating the expres- sion of host cell genes. Thus, it seems that EBV has evolved to use the miRNA pathway for its replicative benefit. From then on, virus-encoded miRNA sequences are reported successively (Griffiths-Jones, 2004). To query whether this strategy is also employed by Hepatitis B virus (HBV) or not, we have analyzed putative miRNA-encoding capacity of HBV. We wondered if HBV maintains RNA structures that resemble pre-miRNAs. As a proof-of-principle, we examined pre-miRNA structures in the genome of HBV. The HBV genome sequence was downloaded from NCBI (accession number: 1476-9271/$ – see front matter © 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.compbiolchem.2007.01.005