Unknown,Transcriptomics,Genomics,Proteomics

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In depth analysis of the interaction of HIV 1 with cellular microRNA biogenesis and effector mechanisms

ABSTRACT: The question of how HIV 1 interfaces with cellular microRNA (miRNA) biogenesis and effector mechanisms has been highly controversial. Here, we first used deep sequencing of small RNAs present in two different infected cell lines (TZM-bl and C8166) and two types of primary human cells (CD4+ PBMCs and macrophages) to unequivocally demonstrate that HIV 1 does not encode any viral miRNAs. Perhaps surprisingly, we also observed that infection of T cells by HIV 1 has only a modest effect on the expression of cellular miRNAs at early times after infection. Comprehensive analysis of miRNA binding to the HIV 1 genome using the photoactivatable ribonucleoside-induced crosslinking and immunoprecipitation (PAR-CLIP) technique revealed several binding sites for cellular miRNAs, a subset of which were shown to be capable of mediating miRNA-mediated repression of gene expression. However, the main finding from this analysis is that HIV 1 transcripts are largely refractory to miRNA binding, most probably due to extensive viral RNA secondary structure. Together, these data demonstrate that HIV 1 neither encodes viral miRNAs nor strongly influences cellular miRNA expression, at least early after infection, and imply that HIV 1 transcripts have evolved to avoid inhibition by pre-existing cellular miRNAs by adopting extensive RNA secondary structures that occlude most potential miRNA binding sites. Small RNA profiling of HIV-1 infected cells through total small RNA deep sequencing and identification of RNA-induced silencing complex (RISC)-associated HIV-1 sequences through the RNP-immunoprecipitation technique of PAR-CLIP on RISC

ORGANISM(S): Homo sapiens

SUBMITTER: Adam Whisnant

PROVIDER: E-GEOD-59944 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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In-depth analysis of the interaction of HIV-1 with cellular microRNA biogenesis and effector mechanisms.

Whisnant Adam W AW Bogerd Hal P HP Flores Omar O Ho Phong P Powers Jason G JG Sharova Natalia N Stevenson Mario M Chen Chin-Ho CH Cullen Bryan R BR

mBio 20130416 2

<h4>Unlabelled</h4>The question of how HIV-1 interfaces with cellular microRNA (miRNA) biogenesis and effector mechanisms has been highly controversial. Here, we first used deep sequencing of small RNAs present in two different infected cell lines (TZM-bl and C8166) and two types of primary human cells (CD4(+) peripheral blood mononuclear cells [PBMCs] and macrophages) to unequivocally demonstrate that HIV-1 does not encode any viral miRNAs. Perhaps surprisingly, we also observed that infection ...[more]

PMID: 23592263

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Dataset Information

In depth analysis of the interaction of HIV 1 with cellular microRNA biogenesis and effector mechanisms

Publications

In-depth analysis of the interaction of HIV-1 with cellular microRNA biogenesis and effector mechanisms.

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