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Review
. 2011 Nov-Dec;1809(11-12):660-7.
doi: 10.1016/j.bbagrm.2011.05.004. Epub 2011 May 17.

Adenovirus and miRNAs

Elena Carnero  1 , James D Sutherland, Puri Fortes
Affiliations
Review

Adenovirus and miRNAs

Elena Carnero et al. Biochim Biophys Acta. 2011 Nov-Dec.

Abstract

Adenovirus infection has a tremendous impact on the cellular silencing machinery. Adenoviruses express high amounts of non-coding virus associated (VA) RNAs able to saturate key factors of the RNA interference (RNAi) processing pathway, such as Exportin 5 and Dicer. Furthermore, a proportion of VA RNAs is cleaved by Dicer into viral microRNAs (mivaRNAs) that can saturate Argonaute, an essential protein for miRNA function. Thus, processing and function of cellular miRNAs is blocked in adenoviral-infected cells. However, viral miRNAs actively target the expression of cellular genes involved in relevant functions such as cell proliferation, DNA repair or RNA regulation. Interestingly, the cellular silencing machinery is active at early times post-infection and can be used to control the adenovirus cell cycle. This is relevant for therapeutic purposes against adenoviral infections or when recombinant adenoviruses are used as vectors for gene therapy. Manipulation of the viral genome allows the use of adenoviral vectors to express therapeutic miRNAs or to be silenced by the RNAi machinery leading to safer vectors with a specific tropism. This article is part of a "Special Issue entitled:MicroRNAs in viral gene regulation".

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Figures

Fig. 1
Fig. 1
A. Schematic of adenovirus genome. The alternative splicing of E1a pre-mRNA is shown. U-rich stretches are indicated. Arrows represent direction of transcription. MLP is the major late promoter. E genes are early and L genes are late. B. Structure of adenovirus type 2 VA I RNA. The structure is divided into three regions associated to the indicated functions. The arrows indicate Dicer cleavage sites for mivaRNAI-137 and mivaRNAI-138.
Fig. 2
Fig. 2
Schematic of mivaRNA biogenesis. VA RNA is transcribed from the viral genome by cellular polymerase (pol) III and is transported to the cytoplasm by Exp5. There, VA RNA binds Dicer and is processed to mivaRNAs able to bind Ago and regulate the expression of target genes. VA RNA is expressed to high levels and saturates Exp5, Dicer and Ago.
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