Down-Regulation of a Host MicroRNA by a
            <i>Herpesvirus saimiri</i>
            Noncoding RNA

Cazalla, Demián; Yario, Therese A.; Steitz, Joan A.

doi:10.1126/science.1187197

Cited by 438 publications

(447 citation statements)

References 25 publications

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“…4a) also attenuated mitochondrial fission (Fig. 4e, upper panel), apoptosis ( ARTICLE endogenous sponge RNA to interact with miRNAs and influence the expression of miRNA 22,24,25 . To explore the underlying mechanism responsible for miR-539 upregulation in response to anoxia treatment, we tested whether lncRNA can be involved in the apoptotic pathway of anoxia treatment.…”

Section: Phb2 Is Able To Inhibit Mitochondrial Fission and Apoptosismentioning

confidence: 89%

CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation

et al. 2014

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Abnormal mitochondrial fission participates in the pathogenesis of many diseases. Long non-coding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the regulation of mitochondrial network is unclear. Here we report that a lncRNA, named cardiac apoptosis-related lncRNA (CARL), can suppress mitochondrial fission and apoptosis by targeting miR-539 and PHB2. The results show that PHB2 is able to inhibit mitochondrial fission and apoptosis. miR-539 is responsible for the dysfunction of PHB2 and regulates mitochondrial fission and apoptosis by targeting PHB2. Further, we show that CARL can act as an endogenous miR-539 sponge that regulates PHB2 expression, mitochondrial fission and apoptosis. Our present study reveals a model of mitochondrial fission regulation that is composed of CARL, miR-539 and PHB2. Modulation of their levels may provide a new approach for tackling apoptosis and myocardial infarction.

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Section: Phb2 Is Able To Inhibit Mitochondrial Fission and Apoptosismentioning

confidence: 89%

CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation

et al. 2014

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“…The only other known miRNA inhibitor that has been described in a mammalian system is HSUR-1, a snRNA that mediates miR-27 degradation in HVStransformed T cells (17). A comparison of HSUR-1 and m169 sequences shows identical sequence at the site of base-pairing to nucleotides 2-7 and 16-19 in miR-27.…”

Section: High-throughput Identification Of MCMV Rnas Associated Withmentioning

confidence: 99%

“…Actinomycin D treatment upon infection prevents miR-27 down-regulation, suggesting that an RNA produced during infection might be involved (16). A small nuclear RNA (snRNA) in Herpesvirus saimiri (HVS), HSUR-1, was recently shown to bind to miR-27 and mediate its degradation (17). However, no homolog of HSUR-1 has been identified in other viral families.…”

mentioning

confidence: 99%

Murine cytomegalovirus encodes a miR-27 inhibitor disguised as a target

Libri

Helwak

Miesen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

132

115

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Individual microRNAs (miRNAs) are rapidly down-regulated during conditions of cellular activation and infection, but factors mediating miRNA turnover are poorly understood. Infection of mouse cells with murine cytomegalovirus (MCMV) induces the rapid down-regulation of an antiviral cellular miRNA, miR-27. Here, we identify a transcript produced by MCMV that binds to miR-27 and mediates its degradation. UV-crosslinking and high-throughput sequencing [CRAC (UV-crosslinking and analysis of cDNA)] identified MCMV RNA segments associated with the miRNA-binding protein Argonaute 2 (Ago2). A cluster of hits mapped to a predicted miR-27-binding site in the 3′UTR of the previously uncharacterized ORF, m169. The expression kinetics of the m169 transcript correlated with degradation of miR-27 during infection, and m169 expression inhibited miR-27 functional activity in a reporter assay. siRNA knockdown of m169 demonstrated its requirement for miR-27 degradation following infection and did not affect other host miRNAs. Substitution of the miR-27-binding site in m169 to create complementarity to a different cellular miRNA, miR-24, resulted in down-regulation of only miR-24 following infection. The m169 transcript is cytoplasmic, capped, polyadenylated, and interacts with miRNA-27 through seed pairing: characteristic features of the normal messenger RNA (mRNA) targets of miRNAs. This virus-host interaction reveals a mode of miRNA regulation in which a mRNA directs the degradation of a miRNA. We speculate that RNA-mediated miRNA degradation could be a more general viral strategy for manipulating host cells.V iruses devote a large portion of their genomes to strategies for manipulating host cells and evading antiviral defense mechanisms. Numerous host miRNA-binding sites have been predicted in different viral genomes, but the validity and functional relevance of most predictions remain unclear. The best studied miRNA-virus interactions demonstrate that RNA viruses can use cellular miRNAs to regulate their life cycles; for example, the interaction between hepatitis C virus and miR-122 enhances viral replication (1), whereas the interaction between HIV-1 and miR-29 mediates its localization to P bodies (2). Direct interactions between host miRNAs and viral genes can also suppress viral gene expression and replication (3-6) (reviewed in Ref. 7). However, the factors driving the evolution of these interactions remain somewhat controversial, because they may relate to viral mechanisms for persistence and latency rather than host defense (8, 9). At the same time, the expression levels of specific miRNAs can indirectly influence infections; miRNAs are key components of the innate immune response (10, 11) and exert antiviral properties by modulating host cofactors and pathways required by viruses (12-15). We previously showed that miR-27 limits the replication capacity of murine cytomegalovirus (MCMV) but is rapidly degraded during the lytic infection (16). Actinomycin D treatment upon infection prevents miR-27 down-regulation, suggest...

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“…Toutefois, l'addition de miR-122 dans ces cellules traitées par les inhibiteurs de la traduction n'augmente pas le taux d'ARNg néosynthétisé, ce qui indique que la synthèse des protéines est néan-moins une étape nécessaire. À partir de ces données, les auteurs émettent l'hypothèse selon laquelle miR-122 pourrait jouer le même rôle que la puromycine, « ceARN » [13], mais aussi dans le cas de génomes viraux comme ceux du cytomégalovirus et des herpes virus [14,15]. Cependant, le VHC ajoute un niveau de régulation encore plus subtil à ce mécanisme, puisqu'il utilise aussi miR-122 pour sa réplication, ce qui provoque une augmentation du nombre de copies de l'ARNg, qui ne font qu'augmenter sa capacité à séquestrer miR-122.…”

Section: Nouvelle Mir-122 Continue De Nous Surprendreunclassified

miR-122 continue de nous surprendre

Mengardi

Ohlmann

2015

Med Sci (Paris)

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Down-Regulation of a Host MicroRNA by a Herpesvirus saimiri Noncoding RNA

Cited by 438 publications

References 25 publications

CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation

CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation

Murine cytomegalovirus encodes a miR-27 inhibitor disguised as a target

miR-122 continue de nous surprendre

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