Cytosine methylation by DNMT2 facilitates stability and survival of HIV-1 RNA in the host cell during infection.
Biochem J
; 474(12): 2009-2026, 2017 06 06.
Article
em En
| MEDLINE
| ID: mdl-28476776
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
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RNA Viral
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Processamento Pós-Transcricional do RNA
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HIV-1
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Citosina
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DNA (Citosina-5-)-Metiltransferases
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Interações Hospedeiro-Patógeno
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article