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Rachana, R.D. and Ganji, Rakesh and Singh, S.P. and Mahalingam, S. and Banerjee, Sharmistha and Khosla, Sanjeev (2017) Cytosine methylation by DNMT2 facilitates stability and survival of HIV-1 RNA in the host cell during infection. Biochemical Journal, 474 (12). pp. 2009-2026. 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 associated with RNA processing proteins. In this study, we show that DNMT2 binds and methylates 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 to 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-1 viral titre. This would suggest that HIV hijacks the RNA processing machinery within the stress granules to ensure its own 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
Depositing User: Dr P Divakar
Date Deposited: 12 May 2017 07:16
Last Modified: 18 Aug 2017 04:41
URI: http://cdfd.sciencecentral.in/id/eprint/778

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