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Cytosine methylation by DNMT2 facilitates stability and survival of HIV-1 RNA in the host cell during infection

Dev, Rachana Roshan (2017) Cytosine methylation by DNMT2 facilitates stability and survival of HIV-1 RNA in the host cell during infection. Biochemical Journal. ISSN 0264-6021

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Abstract

The enigmatic methyltransferase, DNMT2, structurally resembles a DNA methyltransferase but has been shown to be a tRNA methyltransferase targeting cytosine within a specific CpG in different tRNA molecules. We had previously shown that, during environmental stress conditions, DNMT2 is relocalized from the nucleus to the cytoplasmic stress granules and is associatedwith RNA processing proteins. In this study, we show that DNMT2 can binds and methylate various mRNA species in a sequence-independent manner and gets relocalized to stress granules in a phosphorylation dependent manner. Importantly, our results indicate that HIV-1 enhances its survivability in the host cell by utilizing this RNA methylation capability of DNMT2 tq increase stability of its own genome. Upon infection, DNMT2 relocalizes from the nucleus to the stress granules and methylates HIV-1 RNA. This DNMT2-dependent methylation provided post-transcriptional stability to the HIV-1 RNA. Furthermore, DNMT2 overexpression increased the HIV viral titre. This would suggest that HIV ~ijacks the RNA processing machinery within the stress granules to ensure its ownn survival in the host cell. Thus, our findings provide for a novel mechanism by which virus tries to modulate the host cell machinery to its own advantage.

Item Type: Article
Subjects: Research > Research Center - Health Sciences
Depositing User: KMC Manipal
Date Deposited: 25 May 2017 03:56
Last Modified: 25 May 2017 03:56
URI: http://eprints.manipal.edu/id/eprint/148956

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