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Kapoor, R. and Arora, S. and Ponia, S.S. and Kumar, B. and Subba Reddy, Maddika and Banerjea, A.C. (2015) The miRNA miR-34a enhances HIV-1 replication by targeting PNUTS/PPP1R10, which negatively regulates HIV-1 transcriptional complex formation. Biochemical Journal, 470 (3). pp. 293-302. ISSN 1470-8728

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Abstract

HIV-1 relies heavily on the host cellular machinery for its replication.During infection, HIV-1 is known to modulate the host cell microRNA profile. One of the microRNAs, microRNA34a (miR34a) is upregulated by HIV-1 in T cells as suggested by microRNA microarray studies. However, the functional consequences and the mechanism behind this phenomenon was not explored.The present study shows that HIV-1 enhances miR34a in a time-dependentmanner in T cells. Our overexpression and knockdown based experimental results suggest that miR34a promotes HIV-1 replication in T cells. Hence, there exists a positive feedback loop between miR34a and HIV-1 replication. We show that the mechanism of action of miR34a on HIV-1 replication involves a cellular protein, Phosphatase 1 Nuclear Targeting Subunit (PNUTS). PNUTS expression levels decrease with the progression of HIV-1 infection in T cells. Also, the overexpression of PNUTS potently inhibits HIV-1 replication in a dose-dependent manner. We report for the first time that PNUTS negatively regulates HIV-1 transcription by inhibiting the assembly of core components of P-TEFb i.e. CyclinT1 and CDK9.Thus,HIV-1 increases miR34a expression in cells to overcome the inhibitory effect of PNUTS on HIV-1 transcription. So, this work provides new mechanistic details with regard to our understanding of a complex interplay between miR34a and HIV-1 transcription machinery involving PNUTS.

Item Type: Article
Depositing User: Dr P Divakar
Date Deposited: 20 Jul 2015 06:23
Last Modified: 05 Oct 2017 07:05
URI: http://cdfd.sciencecentral.in/id/eprint/260

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