Interferon modulation of cellular microRNAs as an antiviral mechanism

Pedersen, Irene M.; Cheng, Guofeng; Wieland, Stefan; Volinia, Stefano; Croce, Carlo M.; Chisari, Francis V.; David, Michael

doi:10.1038/nature06205

Cited by 804 publications

(739 citation statements)

References 26 publications

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“…We demonstrated that IFN-␣/␤ treatment of monocytes induced the expression of anti-HIV miRNAs ( Figure 2C). This finding supports the studies by others 36,43,44 showing that IFN-␣/␤ is the potent inducer of miRNAs in several cell systems. However, this IFN-mediated anti-HIV innate immunity in monocytes was dampened by morphine treatment (Figure 2C).…”

Section: Discussionsupporting

confidence: 92%

“…A recent study 36 has shown that type I IFNs modulate miRNA expression as an antiviral mechanism. We demonstrated that IFN-␣/␤ treatment of monocytes induced the expression of anti-HIV miRNAs ( Figure 2C).…”

Section: Discussionmentioning

confidence: 99%

“…46 In support of these findings, we demonstrated that morphine treatment inhibited the expression of both IFN-␣ and IFN-␤ in monocytes (data not shown). Because type I IFNs have the ability to induce the expression of antiviral miRNAs, 36 it is likely that the down-regulation of anti-HIV miRNAs by Figure 3. Effect of heroin use on anti-HIV miRNA expression in PBMCs.…”

Section: Discussionmentioning

confidence: 99%

“…36 We next examined the impact of morphine on the expression of IFN-␣/␤-induced miRNAs in monocytes. When treated with IFN-␣ or IFN-␤, monocytes expressed higher levels of anti-HIV miRNAs (miRNA-28, miRNA-125b, miRNA-150, and miRNA-382) compared with untreated cells ( Figure 2C).…”

Section: Morphine Inhibits Ifn-␣/␤-induced Anti-hiv Mirnasmentioning

confidence: 99%

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Inhibition of Anti-HIV MicroRNA Expression

Wang

Zhou

et al. 2011

The American Journal of Pathology

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Several micro RNAs (miRNAs) have the ability to inhibit HIV replication in target cells. Thus, we investigated the impact of opioids (morphine and heroin), widely abused drugs among people infected with HIV, on the expression of cellular anti-HIV miRNAs in monocytes. We found that morphine-treated monocytes expressed lower levels of cellular anti-HIV miRNAs than untreated cells. In addition, morphine treatment of monocytes compromised type I interferon (IFN)-induced anti-HIV miRNA expression. These findings paralleled the observation that morphine treatment of monocytes enhanced HIV replication. These morphine-mediated actions on the anti-HIV miRNAs and HIV could be antagonized by the opioid receptor antagonists (naltrexone or Cys2, Tyr3, Arg5, Pen7-amide). Furthermore, the in vitro impact of morphine on miRNA expression was confirmed by the in vivo observation that heroin-dependent subjects had significantly lower levels of anti-HIV miRNAs (miRNA-28, 125b, 150, and 382) in peripheral blood mononuclear cells than the healthy subjects. These in vitro and in vivo findings indicate that opioid use impairs intracellular innate anti-HIV mechanism(s) in monocytes, contributing to cell susceptibility to HIV infection. (Am J

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Morphine Inhibits Ifn-␣/␤-induced Anti-hiv Mirnasmentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of Anti-HIV MicroRNA Expression

Wang

Zhou

et al. 2011

The American Journal of Pathology

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“…We have shown previously that miRs can directly target hepatitis C viral RNA to repress viral replication 33 , thus raising the possibility that miRs could similarly repress L1 activity in hypomethylated somatic cells. Furthermore, depletion of three of the main proteins involved in miR biogenesis and miR function (Dicer, DGCR8 and Ago) in different cell types results in significantly increased L1 activity 26,27 .…”

Section: Identification Of Retrotransposition-repressor Mirsmentioning

confidence: 99%

miR-128 represses L1 retrotransposition by binding directly to L1 RNA

Hamdorf

Idica

Zisoulis

et al. 2015

Nat Struct Mol Biol

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VOLUME 22 NUMBER 10 OCTOBER 2015 nature structural & molecular biology a r t i c l e s microRNAs (miRs) are a class of small (~22-nt) genomically encoded molecules that inhibit translational initiation and stimulate decay of mRNA targets 1,2 . miRs are transcribed by RNA polymerase II and processed by the RNase III enzymes-Dicer and Drosha with its binding partner, DGCR8-to produce short double-stranded RNAs in the nucleus. One strand associates with the Argonaute (Ago) protein, thus forming the miR-mediated silencing complex (miRISC). miRs guide the pairing of miRISC, with imperfect complementarity, to sequences in target mRNAs, thus resulting in their subsequent destabilization and translational repression of the target 3 . The 'seed sequence' , at nucleotides 2-8, is a key determinant for miRISC-target recognition 4,5 . Recent data have shown that 35-40% of miR-binding sites are found in 3′ untranslated regions (UTRs), 40-50% in coding regions and <5% in 5′-UTR regions of mRNAs 6,7 . More than 60% of the human transcriptome has been predicted to be under miR regulation, thus making this post-transcriptional control pathway as important as protein pathways in the regulation of cell functions 2 . It is clear that miRs have essential roles in regulating diverse functions in normal and diseased cells 8,9 .L1 belongs to the most abundant class of autonomous transposable elements 10 . Human L1 contains two open reading frames, ORF1 and ORF2, which encode a protein with RNA-binding and nucleotide acid-chaperone activity (ORF1) 11 and a protein with endonuclease and reverse-transcriptase activities (ORF2) 12-15 , respectively. L1 mobilizes replicatively from one location in the genome to another by a 'copy-and-paste' mechanism, and it has been proposed to be a remnant of an ancient retrovirus 12,16 . Active and inactive L1s have been implicated in the evolution of mammalian genomes and are linked to cell-based diseases, including cancer [17][18][19] . In addition, somatic L1 insertions are biased toward regions of cancer-specific DNA hypomethylation, thus suggesting that L1 insertions may provide a selective advantage during tumorigenesis 20 . Mechanisms that operate at different levels in gene-expression hierarchies have been selected to control transposition-mediated mutagenesis and mitigate the potential negative effects of newly inserted elements. In germ cells, a specific small-RNA subtype (piwi-interacting RNAs (piRNAs)) efficiently counteracts L1 activity, but these RNAs are not expressed in nongerm cells 21,22 . Somatic cells attenuate element mobilization by DNA methylation of the L1 promoter 23 . Other methods of regulation are mediated by APOBEC proteins 24,25 , microprocessor interactions 26 and Ago-mediated RNA interference in mouse embryonic stem cells 27 . L1-promoter silencing is greatly attenuated, and L1 transcription is reactivated in hypomethylated cells, such as cancer cells and tumor-initiating cells, and is also reactivated during reprogramming [28][29][30] . Because miRs act as regulators of g...

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RNA Silencing and its Suppressors in the Plant‐virus Interplay

Vallí

López‐Moya

Garcı́a

2009

Encyclopedia of Life Sciences

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Viruses are obligate intracellular parasites that need to evade the host defences targeted against them. In plants, activation of ribonucleic acid (RNA) silencing is among the most powerful responses against viruses. To overcome this defence, both deoxyribonucleic acid (DNA) and RNA plant viruses make use of viral products able to interfere with silencing mechanisms, and known collectively as RNA silencing suppressors (RSSs). RSSs present an extraordinary diversity in modes of action, and therefore, their study is providing valuable information about the different silencing pathways in plants. This article reviews our knowledge on RSSs, including the experimental systems used to identify them, and the mechanisms by which they act. Finally, the additional effects that they cause in the network of silencing pathways, and hence the need of a tight control of their activity, are also considered. Key concepts: Argonaute: Family of proteins that contain certain conserved domains, such as PIWI domain (found in Piwi, or P‐element‐induced wimpy testis in Drosophila , and related proteins) and PAZ domain (found in Piwi, Argonaute and Zwille proteins). Proteins of this family are the main components of RNA silencing effector complexes. Dicer: Ribonuclease belonging to the RNase III family. Dicer‐like enzymes cleave hairpin or double‐strand RNA molecules into short RNA duplexes of 20–24 nucleotides with a 2‐nucleotides overhang at the 3′ ends, which are key components of the RNA silencing pathways. microRNA (miRNA): Endogenous single‐strand RNA of 20–21 nucleotides, which derives from a hairpin precursor. miRNAs are incorporated into RISC, guiding it, by base complementary, to silence endogenous mRNAs. RNA‐dependent RNA polymerase (RdRP, RDR): Enzyme able to synthesize RNA using RNA as template. These enzymes are involved in amplification steps of RNA silencing. RNA‐induced silencing complex (RISC): Multicomponent complex including an Argonaute protein and a short RNA. RISC can silence mRNAs by endonucleolytic cleavage, decay acceleration and translation inhibition. RNA‐induced transcriptional silencing complex (RITS): Multicomponent complex including an Argonaute protein and a short RNA that silence gene expression by inhibiting or downregulating the transcription activity. RNA silencing: General term used to describe different events triggered by small RNAs to induce transcriptional or posttranscriptional gene downregulation in a sequence‐homology manner. RNA silencing suppressor (RSS): Factor (usually a protein) with the capacity to interfere with the onset of RNA silencing or with its maintenance. The expression of viral RSSs is the most common strategy that plant viruses use to escape from RNA silencing. Short interfering RNA (siRNA): Small RNA of 20–24 nucleotides derived from Dicer‐mediated cleavage of a double‐stranded RNA precursor. One of the strands of the siRNA is incorporated in RISC or RITS to guide their RNA silencing effector activities.

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Interferon modulation of cellular microRNAs as an antiviral mechanism

Cited by 804 publications

References 26 publications

Inhibition of Anti-HIV MicroRNA Expression

Inhibition of Anti-HIV MicroRNA Expression

miR-128 represses L1 retrotransposition by binding directly to L1 RNA

RNA Silencing and its Suppressors in the Plant‐virus Interplay

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