HIV-1 encoded candidate micro-RNAs and their cellular targets - PubMed (original) (raw)

Comparative Study

HIV-1 encoded candidate micro-RNAs and their cellular targets

Yamina Bennasser et al. Retrovirology. 2004.

Abstract

MicroRNAs (miRNAs) are small RNAs of 21-25 nucleotides that specifically regulate cellular gene expression at the post-transcriptional level. miRNAs are derived from the maturation by cellular RNases III of imperfect stem loop structures of ~ 70 nucleotides. Evidence for hundreds of miRNAs and their corresponding targets has been reported in the literature for plants, insects, invertebrate animals, and mammals. While not all of these miRNA/target pairs have been functionally verified, some clearly serve roles in regulating normal development and physiology. Recently, it has been queried whether the genome of human viruses like their cellular counterpart also encode miRNA. To date, there has been only one report pertaining to this question. The Epstein-Barr virus (EBV) has been shown to encode five miRNAs. Here, we extend the analysis of miRNA-encoding potential to the human immunodeficiency virus (HIV). Using computer-directed analyses, we found that HIV putatively encodes five candidate pre-miRNAs. We then matched deduced mature miRNA sequences from these 5 pre-miRNAs against a database of 3' untranslated sequences (UTR) from the human genome. These searches revealed a large number of cellular transcripts that could potentially be targeted by these viral miRNA (vmiRNA) sequences. We propose that HIV has evolved to use vmiRNAs as a means to regulate cellular milieu for its benefit.

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Figures

Figure 1

Figure 1

Sequences and localization of HIV-encoded miRNA candidates. a) Locations for 5 predicted pre-miRNAs candidates in the pNL4-3 genome are shown. b) The folded structures of the 5 viral pre-miRNAs from pNL4-3 (Accession Number AF 324493) [17] are illustrated. Folded pre-miRNAs and their corresponding predicted mature viral miRNA (red) are listed. Nucleotide positions (where 1 is the initiation of transcription) in the pNL4-3 genome are presented in the right column.

Figure 2

Figure 2

Potential cellular targets for each of the vmiRNAs. The two deduced mature vmiRNAs predicted from each precursor miRNA are shown. The mature vmiRNA sequences were individually searched against a database of human 3'UTRs using imperfect complementarity criteria as described in the text. The number of potential candidate cellular RNA targets is enumerated. Most of the cellular targets are incompletely characterized expressed sequence tag (EST) clones, with a subset of targets being known genes. For each predicted vmiRNA, we list two examples of known cellular gene targets at the right. A full list of targets is available upon request.

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