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

Rachana Roshan Dev; Rakesh Ganji; Satya Prakash Singh; Sundarasamy Mahalingam; Sharmistha Banerjee; Sanjeev Khosla

doi:10.1042/bcj20170258

journal article Jun 06, 2017

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

Rachana Roshan Dev Rakesh Ganji Satya Prakash Singh

Sundarasamy Mahalingam Sharmistha Banerjee Sanjeev Khosla

Biochemical Journal Vol. 474 No. 12 pp. 2009-2026 · Portland Press Ltd.

View at Publisher Save 10.1042/bcj20170258

Abstract

The enigmatic methyltransferase, DNMT2 (DNA methyltransferase 2), 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 re-localized from the nucleus to the cytoplasmic stress granules (SGs) and is associated with RNA-processing proteins. In the present study, we show that DNMT2 binds and methylates various mRNA species in a sequence-independent manner and gets re-localized to SGs 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 the stability of its own genome. Upon infection, DNMT2 re-localizes from the nucleus to the SGs 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 SGs 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.

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Details

Published: Jun 06, 2017
Vol/Issue: 474(12)
Pages: 2009-2026

Authors

R

Rachana Roshan Dev

Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad 500001, India; Graduate Studies, Manipal University, Manipal 576104, India

R

Rakesh Ganji

Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India

S

Satya Prakash Singh

Laboratory of Molecular Virology and Cell Biology, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India

S

Sundarasamy Mahalingam

Laboratory of Molecular Virology and Cell Biology, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India

S

Sharmistha Banerjee

Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India

S

Sanjeev Khosla

Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad 500001, India

Cite This Article

Rachana Roshan Dev, Rakesh Ganji, Satya Prakash Singh, et al. (2017). Cytosine methylation by DNMT2 facilitates stability and survival of HIV-1 RNA in the host cell during infection. Biochemical Journal, 474(12), 2009-2026. https://doi.org/10.1042/bcj20170258

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

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