GW body disassembly triggered by siRNAs independently of their silencing activity

Šerman, Alan; Roy, Florence Le; Aigueperse, Christelle; Kress, Michel; Dautry, François; Weil, Dominique

doi:10.1093/nar/gkm491

Cited by 78 publications

(107 citation statements)

References 37 publications

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“…To further exclude the possibility that the defects in the innate response in LSm14A knockdown cells are due to disrupting the function of the P-bodies, we designed two RNAi vectors for DDX6 (also named p54), which is a critical component of the P-bodies, and knockdown of DDX6 leads to disassembly of the P-bodies (22,23). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

LSm14A is a processing body-associated sensor of viral nucleic acids that initiates cellular antiviral response in the early phase of viral infection

Liu

Chen

Zhou

et al. 2012

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

132

125

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Recognition of viral nucleic acids by pattern recognition receptors initiates type I IFN induction and innate antiviral immune response. Here we show that LSm14A, a member of the LSm family involved in RNA processing in the processing bodies, binds to synthetic or viral RNA and DNA and mediates IRF3 activation and IFN-β induction. Knockdown of LSm14A inhibits cytosolic RNA-and DNA-trigger type I IFN production and cellular antiviral response. Moreover, LSm14A is essential for early-phase induction of IFN-β after either RNA or DNA virus infection. We further found that LSm14A-mediated IFN-β induction requires RIG-I-VISA or MITA after RNA or DNA virus infection, respectively, and viral infection causes translocation of LSm14A to peroxisomes, where RIG-I, VISA, and MITA are located. These findings suggest that LSm14A is a sensor for both viral RNA and DNA and plays an important role in initiating IFN-β induction in the early phase of viral infection.

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Section: Resultsmentioning

confidence: 99%

LSm14A is a processing body-associated sensor of viral nucleic acids that initiates cellular antiviral response in the early phase of viral infection

Liu

Chen

Zhou

et al. 2012

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

132

125

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Section: Introductionmentioning

confidence: 96%

“…In mammals, this reversibility of mRNA localization has been observed for miRNA-mediated mRNA repression in Huh7 cells (Pillai, 2005;Pillai et al, 2005;Bhattacharyya et al, 2006a). Although such a shuttling of mRNAs between polysomes and P-bodies has not been described for other mechanisms of translational regulation, many proteins associated with translational regulation localize in P-bodies, such as 4E-T, CPEB-1, Rck-p54, and RAP55 (Andrei et al, 2005;Wilczynska et al, 2005;Yang et al, 2006;Serman et al, 2007).Hence, in cells which rely on translational control to regulate gene expression, P-bodies or other specialized RNA granules would be expected to be present and play a role in mRNA storage. In early metazoans, the presence of germinal RNA granules has been well documented (Anderson and Kedersha, 2006); they are involved in the timing and localization of mRNA translation to promote germ cell development.…”

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confidence: 96%

Dcp1-Bodies in Mouse Oocytes

Swetloff

Conne

Huarte

et al. 2009

MBoC

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Processing bodies (P-bodies) are cytoplasmic granules involved in the storage and degradation of mRNAs. In somatic cells, their formation involves miRNA-mediated mRNA silencing. Many P-body protein components are also found in germ cell granules, such as in mammalian spermatocytes. In fully grown mammalian oocytes, where changes in gene expression depend entirely on translational control, RNA granules have not as yet been characterized. Here we show the presence of P-body-like foci in mouse oocytes, as revealed by the presence of Dcp1a and the colocalization of RNAassociated protein 55 (RAP55) and the DEAD box RNA helicase Rck/p54, two proteins associated with P-bodies and translational control. These P-body-like structures have been called Dcp1-bodies and in meiotically arrested primary oocytes, two types can be distinguished based on their size. They also have different protein partners and sensitivities to the depletion of endogenous siRNA/miRNA and translational inhibitors. However, both type progressively disappear during in vitro meiotic maturation and are virtually absent in metaphase II-arrested secondary oocytes. Moreover, this disassembly of hDcp1a-bodies is concomitant with the posttranslational modification of EGFP-hDcp1a. INTRODUCTIONGene expression flows from DNA to protein using mRNA as an intermediate. Transcripts can either be used immediately as template for protein synthesis or translationally silenced and stored for later translation. A subset of silenced mRNAs is packaged into microscopically visible RNP granules that lack a limiting lipid membrane (Kedersha and Anderson, 2007). In mammals, processing bodies (P-bodies) RNA granules are present in a broad range of somatic cell types, including highly specialized cells such as neurons. Initially, P-bodies were discovered as 5Ј-3Ј mRNA decay centers in mammalian somatic cells (Bashkirov et al., 1997;Eystathioy et al., 2003;Cougot et al., 2004), and were found to be conserved in yeast (Sheth and Parker, 2003); because of the systematic localization of the decapping protein Dcp1a in P-bodies, they were also called Dcp1-bodies. Subsequently, P-bodies were shown to be involved in mRNA surveillance (Chen and Shyu, 2003;Couttet and Grange, 2004), RNAmediated silencing (Rehwinkel et al., 2005;Jakymiw et al., 2005;Liu et al., 2005a), and translational control Liu et al., 2005b;Bhattacharyya et al., 2006b).A role for P-bodies in translational control was first highlighted in yeast cells. It was shown that the entry of an mRNA into P-bodies does not automatically lead to its degradation: upon glucose starvation mRNAs can be temporarily stored in P-bodies, which increase in size and number, and then exit the foci upon refeeding to reenter polysomes (Brengues et al., 2005). In mammals, this reversibility of mRNA localization has been observed for miRNA-mediated mRNA repression in Huh7 cells (Pillai, 2005;Pillai et al., 2005;Bhattacharyya et al., 2006a). Although such a shuttling of mRNAs between polysomes and P-bodies has not been described for other mecha...

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“…This suggests that although microscopic P-bodies are not necessarily required for RNAi, silencing could occur in submicroscopic complexes that might then trigger the assembly of larger, microscopic structures. A recent study noted that P-body disassembly was induced by a range of siRNAs, whose targets were not related to mRNA metabolism and P-body components (Serman et al, 2007), indicating that the structure and function of P-bodies are more complex than currently believed. These conflicting results led us to further examine the relationship between siRNA and P-bodies.…”

Section: Introductionmentioning

confidence: 99%

Localization of Double-stranded Small Interfering RNA to Cytoplasmic Processing Bodies Is Ago2 Dependent and Results in Up-Regulation of GW182 and Argonaute-2

Jagannath

Wood

2009

MBoC

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Processing bodies (P-bodies) are cytoplasmic foci implicated in the regulation of mRNA translation, storage, and degradation. Key effectors of microRNA (miRNA)-mediated RNA interference (RNAi), such as Argonaute-2 (Ago2), miRNAs, and their cognate mRNAs, are localized to these structures; however, the precise role that P-bodies and their component proteins play in small interfering RNA (siRNA)-mediated RNAi remains unclear. Here, we investigate the relationship between siRNA-mediated RNAi, RNAi machinery proteins, and P-bodies. We show that upon transfection into cells, siRNAs rapidly localize to P-bodies in their native double-stranded conformation, as indicated by fluorescence resonance energy transfer imaging and that Ago2 is at least in part responsible for this siRNA localization pattern, indicating RISC involvement. Furthermore, siRNA transfection induces up-regulated expression of both GW182, a key P-body component, and Ago2, indicating that P-body localization and interaction with GW182 and Ago2 are important in siRNA-mediated RNAi. By virtue of being centers where these proteins and siRNAs aggregate, we propose that the P-body microenvironment, whether as microscopically visible foci or submicroscopic protein complexes, facilitates siRNA processing and siRNA-mediated silencing through the action of its component proteins. INTRODUCTIONRNA interference (RNAi) is a powerful homology-based gene silencing mechanism directed by small RNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs). RNAi is a posttranscriptional process, leading to either translational repression of the target mRNA, typical of miRNAmediated silencing, or degradation of the target via siRNAmediated silencing (Hammond, 2005). Recently, several components of the RNAi pathway, including Argonaute proteins (Sen and Blau, 2005), miRNAs, and their targets (Liu et al., 2005b;Pillai et al., 2005) have been localized to processing bodies (P-bodies). P-bodies are recognized as important cytoplasmic mRNA processing centers where nontranslating mRNA is sorted and either stored, repressed, or degraded (for review, see Eulalio et al., 2007a). Enzymes associated with mRNA degradation, such the CCR4-CAF-1-Not complex involved in deadenlyation (Cougot et al., 2004); DCP1 and -2 (van Dijk et al., 2002) involved in decapping; and XRN-1, a 5Ј-3Ј exonuclease (Ingelfinger et al., 2002), have all been localized to P-bodies. These foci also contain proteins involved in nonsense-mediated decay (Sheth and Parker, 2006) and AU-rich element-mediated mRNA decay pathways (Vasudevan and Steitz, 2007).Although it is clear that RNAi and P-bodies are associated, the precise role of P-bodies in RNAi remains unclear. There is evidence that P-body components are essential for miRNA-based gene silencing. Depletion of certain P-body components, including RCK/P54 (Chu and Rana, 2006) and GW182 in human (Liu et al., 2005a) and Drosophila (Rehwinkel et al., 2005) cells leads to a loss of silencing. Furthermore, the decay of miRNA targets seems to require the de...

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GW body disassembly triggered by siRNAs independently of their silencing activity

Cited by 78 publications

References 37 publications

LSm14A is a processing body-associated sensor of viral nucleic acids that initiates cellular antiviral response in the early phase of viral infection

LSm14A is a processing body-associated sensor of viral nucleic acids that initiates cellular antiviral response in the early phase of viral infection

Dcp1-Bodies in Mouse Oocytes

Localization of Double-stranded Small Interfering RNA to Cytoplasmic Processing Bodies Is Ago2 Dependent and Results in Up-Regulation of GW182 and Argonaute-2

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