Stimulation of Hepatitis C Virus RNA translation by microRNA-122 occurs under different conditions in vivo and in vitro

Goergen, Dagmar; Niepmann, Michael

doi:10.1016/j.virusres.2012.05.022

Cited by 22 publications

(30 citation statements)

References 43 publications

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“…In structural terms, this long-range RNA-RNA interaction can switch the conformation of the HCV 5′-UTR from an "open" to a "closed" conformation, and this structural switch was shown in vitro to be relieved by the single-stranded mature miR-122 guide strand that interferes with the long-range interaction [29]. Recently, we have confirmed the functional implications of the above structural study by showing that single-stranded miR-122 as well as actually any single-stranded RNA oligonucleotide that can interfere with the inhibitory long-range RNA-RNA interaction stimulates translation of a HCV reporter RNA in reticulocyte lysate [30].…”

Section: Introductionmentioning

confidence: 62%

microRNA-122 Dependent Binding of Ago2 Protein to Hepatitis C Virus RNA Is Associated with Enhanced RNA Stability and Translation Stimulation

et al. 2013

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Translation of Hepatitis C Virus (HCV) RNA is directed by an internal ribosome entry site (IRES) in the 5′-untranslated region (5′-UTR). HCV translation is stimulated by the liver-specific microRNA-122 (miR-122) that binds to two binding sites between the stem-loops I and II near the 5′-end of the 5′-UTR. Here, we show that Argonaute (Ago) 2 protein binds to the HCV 5′-UTR in a miR-122-dependent manner, whereas the HCV 3′-UTR does not bind Ago2. miR-122 also recruits Ago1 to the HCV 5’-UTR. Only miRNA duplex precursors of the correct length stimulate HCV translation, indicating that the duplex miR-122 precursors are unwound by a complex that measures their length. Insertions in the 5′-UTR between the miR-122 binding sites and the IRES only slightly decrease translation stimulation by miR-122. In contrast, partially masking the miR-122 binding sites in a stem-loop structure impairs Ago2 binding and translation stimulation by miR-122. In an RNA decay assay, also miR-122-mediated RNA stability contributes to HCV translation stimulation. These results suggest that Ago2 protein is directly involved in loading miR-122 to the HCV RNA and mediating RNA stability and translation stimulation.

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Section: Introductionmentioning

confidence: 62%

microRNA-122 Dependent Binding of Ago2 Protein to Hepatitis C Virus RNA Is Associated with Enhanced RNA Stability and Translation Stimulation

et al. 2013

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“…17 was reported to be involved in repressing HCV translation. This interaction can be relieved in the presence of microRNA-122 which by that can indirectly stimulate translation (Díaz-Toledano et al 2009;Goergen and Niepmann 2012). In contrast, a possible biological role of the proposed interactions No.…”

Section: Resultsmentioning

confidence: 97%

Conserved RNA secondary structures and long-range interactions in hepatitis C viruses

Fricke

Dünnes

Zayas

et al. 2015

RNA

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Hepatitis C virus (HCV) is a hepatotropic virus with a plus-strand RNA genome of ∼9.600 nt. Due to error-prone replication by its RNA-dependent RNA polymerase (RdRp) residing in nonstructural protein 5B (NS5B), HCV isolates are grouped into seven genotypes with several subtypes. By using whole-genome sequences of 106 HCV isolates and secondary structure alignments of the plus-strand genome and its minus-strand replication intermediate, we established refined secondary structures of the 5 ′ untranslated region (UTR), the cis-acting replication element (CRE) in NS5B, and the 3 ′ UTR. We propose an alternative structure in the 5 ′ UTR, conserved secondary structures of 5B stem-loop (SL)1 and 5BSL2, and four possible structures of the X-tail at the very 3 ′ end of the HCV genome. We predict several previously unknown long-range interactions, most importantly a possible circularization interaction between distinct elements in the 5 ′ and 3 ′ UTR, reminiscent of the cyclization elements of the related flaviviruses. Based on analogy to these viruses, we propose that the 5 ′ -3 ′ UTR base-pairing in the HCV genome might play an important role in viral RNA replication. These results may have important implications for our understanding of the nature of the cis-acting RNA elements in the HCV genome and their possible role in regulating the mutually exclusive processes of viral RNA translation and replication.

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“…As mentioned above, miRNA-122 plays a critical role in HCV life cycle [29,30,60,140]. Interestingly, HIV-1 infection of T cell lines, significantly up-regulated the expression of miR-122 [141].…”

Section: Potential Role Of Mirnas In Hcv/hiv-1 Co-infectionmentioning

confidence: 99%

MicroRNAs, Hepatitis C Virus, and HCV/HIV-1 Co-Infection: New Insights in Pathogenesis and Therapy

Gupta

Swaminathan

Martín-García

et al. 2012

Viruses

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MicroRNAs (miRNAs) can exert a profound effect on Hepatitis C virus (HCV) replication. The interaction of HCV with the highly liver-enriched miRNA, miR-122 represents one such unique example of viruses having evolved mechanism(s) to usurp the host miRNA machinery to support viral life cycle. Furthermore, HCV infection can also trigger changes in the cellular miRNA profile, which may ultimately contribute to the outcome of viral infection. Accumulating knowledge on HCV-host miRNA interactions has ultimately influenced the design of therapeutic interventions against chronic HCV infection. The importance of microRNA modulation in Human Immunodeficiency Virus (HIV-1) replication has been reported, albeit only in the context of HIV-1 mono-infection. The development of HCV infection is dramatically influenced during co-infection with HIV-1. Here, we review the current knowledge on miRNAs in HCV mono-infection. In addition, we discuss the potential role of some miRNAs, identified from the analyses of public data, in HCV/HIV-1 co-infection.

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Stimulation of Hepatitis C Virus RNA translation by microRNA-122 occurs under different conditions in vivo and in vitro

Cited by 22 publications

References 43 publications

microRNA-122 Dependent Binding of Ago2 Protein to Hepatitis C Virus RNA Is Associated with Enhanced RNA Stability and Translation Stimulation

microRNA-122 Dependent Binding of Ago2 Protein to Hepatitis C Virus RNA Is Associated with Enhanced RNA Stability and Translation Stimulation

Conserved RNA secondary structures and long-range interactions in hepatitis C viruses

MicroRNAs, Hepatitis C Virus, and HCV/HIV-1 Co-Infection: New Insights in Pathogenesis and Therapy

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