MicroRNAs (miRNAs) are short RNA molecules responsible for post-transcriptional gene silencing by the degradation or translational inhibition of their target messenger RNAs (mRNAs). This process of gene silencing, known as RNA interference (RNAi), is mediated by highly conserved Argonaute (Ago) proteins which are the key components of the RNA induced silencing complex (RISC). In humans, Ago2 is responsible for the endonuclease cleavage of targeted mRNA and it interacts with the mRNAbinding protein GW182, which is a marker for cytoplasmic foci referred to as GW bodies (GWBs). We demonstrated that the antiAgo2 monoclonal antibody 4F9 recognized GWBs in a cell cycle dependent manner and was capable of capturing miRNAs associated with Ago2. Since Ago2 protein is the effector protein of RNAi, anti-Ago2 monoclonal antibody may be useful in capturing functional miRNAs.
There was an error published in J. Cell Sci. 120, 1317-1323.We apologise for two errors that occurred in the online and pdf versions of this article. The printed version is correct.On p. 1317, in the Summary, the sentence 'Formation of GW bodies appears to depend on both specific protein factors and RNA, in particular, microRNA.' appeared twice. The correct version of the summary is shown below. Summary GW bodies, also known as mammalian P-bodies, are cytoplasmic foci involved in the post-transcriptional regulation of eukaryotic gene expression. Recently, GW bodies have been linked to RNA interference and demonstrated to be important for short-interfering-RNA-and microRNA-mediated mRNA decay and translational repression. Evidence indicates that both passenger and guide strands of short-interfering RNA duplexes can localize to GW bodies, thereby indicating that RNA-induced silencing complexes may be activated within these cytoplasmic centers. Work over the past few years has significantly increased our understanding of the biology of GW bodies, revealing that they are specialized cell components that spatially regulate mRNA turnover in various biological processes. Formation of GW bodies appears to depend on both specific protein factors and RNA, in particular, microRNA. Here, we propose a working model for GW body assembly in terms of its relationship to RNA interference. In this process, one or more heteromeric protein complexes accumulate in successive steps into larger ribonucleoprotein structures.On p. 1319, right column, first paragraph, the word order of the penultimate sentence was incorrect and should read:In particular, studies in Drosophila indicate that GW182 interacts with Ago1 and promotes miRNA-mediated degradation of a subset of mRNA targets (Behm-Ansmant et al., 2006). Commentary IntroductionThe control of mRNA stability plays key roles in both the posttranscriptional regulation of eukaryotic gene expression (Keene and Lager, 2005;Wilusz and Wilusz, 2004) and mRNA quality control (Fasken and Corbett, 2005). The latter involves the recognition and rapid degradation of aberrant mRNAs and takes place when translation termination occurs too early (nonsense-mediated decay) or fails to occur (non-stop decay) (Fasken and Corbett, 2005) or when translation elongation stalls (no-go decay) (Doma and Parker, 2006). In eukaryotes, mRNA turnover is regulated by two major mechanisms. One involves the multisubunit exosome, where transcripts are degraded by 3Ј-to-5Ј exonucleases (for a review, see van Hoof and Parker, 1999). The second mechanism involves cytoplasmic compartments termed GW bodies (GWBs), which spatially control mRNA turnover by the 5Ј-to-3Ј mRNA decay machinery. These discrete cytoplasmic foci, also called Dcpcontaining bodies or processing (P)-bodies, constitute sites of mRNA degradation, storage and translational repression (Brengues
BackgroundMicroRNAs (miRNAs) are involved in the regulation of key biological processes and have been implicated in various diseases, including autoimmune disorders. The pathogenesis of polymyositis (PM) and dermatomyositis (DM) is considered to be mediated by autoimmune reactions. To determine miRNA role in the development and progression of PM and DM, we performed plasma miRNA profiling in PM/DM patients before and after treatment.MethodsTotal RNA was isolated from plasma of 10 patients before and after treatment with prednisolone, or, in case of prednisolone resistance or complications, with the combination of calcineurin inhibitors (cyclosporine or tacrolims) and/or pulse intravenous cyclophosphamide. The expression of miRNAs was determined using miRNA microarray and validated by qRT-PCR.ResultsMore differentially expressed miRNAs were found in plasma of DM patients compared to PM patients before and after treatment, and their profiles were different. Among the differentially expressed plasma miRNA identified by microarray, the levels of hsa-miR-4442 were confirmed by qRT-PCR to be significantly decreased by treatment. In addition, plasma hsa-miR-4442 content in active PM/DM significantly exceeded that in other active autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, as well as in healthy individuals. The level of plasma hsa-miR-4442 was positively correlated with Skeletal Disease Activity in MITAX (Myositis Intention to Treat Activity Index).ConclusionThis is the first report describing plasma miRNA expression profiles in PM/DM patients. The present data suggest that plasma levels of miRNAs may be associated with polymyositis/dermatomyositis and hsa-miR-4442 could be used as a biomarker for PM/DM diagnosis and/or disease activity.Electronic supplementary materialThe online version of this article (10.1186/s41232-017-0058-1) contains supplementary material, which is available to authorized users.
There was an error published in J. Cell Sci. 120, 1317-1323.We apologise for two errors that occurred in the online and pdf versions of this article. The printed version is correct.On p. 1317, in the Summary, the sentence 'Formation of GW bodies appears to depend on both specific protein factors and RNA, in particular, microRNA.' appeared twice. The correct version of the summary is shown below. Summary GW bodies, also known as mammalian P-bodies, are cytoplasmic foci involved in the post-transcriptional regulation of eukaryotic gene expression. Recently, GW bodies have been linked to RNA interference and demonstrated to be important for short-interfering-RNA-and microRNA-mediated mRNA decay and translational repression. Evidence indicates that both passenger and guide strands of short-interfering RNA duplexes can localize to GW bodies, thereby indicating that RNA-induced silencing complexes may be activated within these cytoplasmic centers. Work over the past few years has significantly increased our understanding of the biology of GW bodies, revealing that they are specialized cell components that spatially regulate mRNA turnover in various biological processes. Formation of GW bodies appears to depend on both specific protein factors and RNA, in particular, microRNA. Here, we propose a working model for GW body assembly in terms of its relationship to RNA interference. In this process, one or more heteromeric protein complexes accumulate in successive steps into larger ribonucleoprotein structures.On p. 1319, right column, first paragraph, the word order of the penultimate sentence was incorrect and should read:In particular, studies in Drosophila indicate that GW182 interacts with Ago1 and promotes miRNA-mediated degradation of a subset of mRNA targets (Behm-Ansmant et al., 2006).
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