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The Role of GW/P-Bodies in RNA Processing and Silencing Andrew Jakymiw, Kaleb M

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The Role of GW/P-Bodies in RNA Processing and Silencing Andrew Jakymiw, Kaleb M Erratum The role of GW/P-bodies in RNA processing and silencing Andrew Jakymiw, Kaleb M. Pauley, Songqing Li, Keigo Ikeda, Shangli Lian, Theophany Eystathioy, Minoru Satoh, Marvin J. Fritzler and Edward K. L. Chan Journal of Cell Science 120, 1702 (2007) doi:10.1242/jcs.03452 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 1317 The role of GW/P-bodies in RNA processing and silencing Andrew Jakymiw1, Kaleb M. Pauley1, Songqing Li1, Keigo Ikeda1, Shangli Lian1, Theophany Eystathioy2, Minoru Satoh3, Marvin J. Fritzler2 and Edward K. L. Chan1,* 1Department of Oral Biology, University of Florida, Gainesville, FL 32610, USA 2Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, T2N 4N1, Canada 3Division of Rheumatology and Clinical Immunology, Department of Medicine, and Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA *Author for correspondence (e-mail: [email protected]) Accepted 21 February 2007 Journal of Cell Science 120, 1317-1323 Published by The Company of Biologists 2007 doi:10.1242/jcs.03429 Summary GW bodies, also known as mammalian P-bodies, are significantly increased our understanding of the biology of cytoplasmic foci involved in the post-transcriptional GW bodies, revealing that they are specialized cell regulation of eukaryotic gene expression. Recently, GW components that spatially regulate mRNA turnover in bodies have been linked to RNA interference and various biological processes. The formation of GW bodies demonstrated to be important for short-interfering-RNA- appears to depend on both specific protein factors and and microRNA-mediated mRNA decay and translational RNA, in particular, microRNA. Here, we propose a repression. Evidence indicates that both passenger and working model for GW body assembly in terms of its guide strands of short-interfering RNA duplexes can relationship to RNA interference. In this process, one or localize to GW bodies, thereby indicating that RNA- more heteromeric protein complexes accumulate in induced silencing complexes may be activated within these successive steps into larger ribonucleoprotein structures. cytoplasmic centers. Formation of GW bodies appears to depend on both specific protein factors and RNA, in Key words: GW bodies, P-bodies, RNA interference, mRNA particular, microRNA. Work over the past few years has degradation, microRNA, short-interfering RNA Introduction mRNAs (for reviews, see Filipowicz et al., 2005; Meister and Journal of Cell Science The control of mRNA stability plays key roles in both the post- Tuschl, 2004; Rana, 2007; Sen and Blau, 2006; Valencia- transcriptional regulation of eukaryotic gene expression Sanchez et al., 2006). The discovery that RNAi effector proteins (Keene and Lager, 2005; Wilusz and Wilusz, 2004) and mRNA (Jakymiw et al., 2005; Liu et al., 2005a; Liu et al., 2005b; Sen quality control (Fasken and Corbett, 2005). The latter involves and Blau, 2005) and small RNAs localize to GWBs (Jakymiw et the recognition and rapid degradation of aberrant mRNAs and al., 2005; Pauley et al., 2006; Pillai et al., 2005), and that GWB takes place when translation termination occurs too early assembly appears to be required for the proper functioning of the (nonsense-mediated decay) or fails to occur (non-stop decay) RNAi pathway (Jakymiw et al., 2005; Liu et al., 2005a; Meister (Fasken and Corbett, 2005) or when translation elongation et al., 2005), suggests that these foci are specifically involved in stalls (no-go decay) (Doma and Parker, 2006). In eukaryotes, short-interfering RNA (siRNA)- and microRNA (miRNA)- mRNA turnover is regulated by two major mechanisms. One mediated mRNA degradation and/or translational repression†. involves the multisubunit exosome, where transcripts are degraded by 3Ј-to-5Ј exonucleases (for a review, see van Hoof †siRNAs are small RNAs of ~21 nucleotides in length and are derived from the progressive cleavage of long, perfectly complementary double-stranded RNAs (dsRNAs) by an and Parker, 1999). The second mechanism involves RNase-III-type endonuclease, Dicer. They can originate from long dsRNAs transiently cytoplasmic compartments termed GW bodies (GWBs), which introduced into cells by transfection or stably expressed hairpin-containing dsRNA Ј Ј precursors derived from DNA constructs. They assemble into an RNA-protein complex spatially control mRNA turnover by the 5 -to-3 mRNA decay known as the RNA-induced silencing complex (RISC or siRISC), which includes machinery. These discrete cytoplasmic foci, also called Dcp- Argonaute 2 (Ago2), a key component of RNAi that possesses endonuclease activity. containing bodies or processing (P)-bodies, constitute sites of RISC then targets and cleaves perfectly complementary mRNAs, generating 5Ј and 3Ј fragments, which are subsequently degraded. MiRNAs are similar in size to siRNAs but mRNA degradation, storage and translational repression originate from hairpin-containing precursors encoded by the genome. These non-coding (Brengues et al., 2005; Coller and Parker, 2005; Cougot et al., precursors of miRNAs have double-stranded regions with imperfect complementarity and 2004; Eystathioy et al., 2002; Eystathioy et al., 2003; Sheth are sequentially processed by RNase-III-type enzymes Drosha and Dicer into mature miRNAs. The mature miRNAs then assemble into an RNA-protein complex referred to and Parker, 2003; Van Dijk et al., 2002). Recently, they have as the miRNA ribonucleoprotein complex (miRNP or miRISC), which is structurally also been shown to function in RNA interference (RNAi) similar to RISC and contains at least one Argonaute protein. Multiple copies of miRNPs are directed to the 3Ј-UTR of certain mRNAs that have imperfect complementarity to the (Jakymiw et al., 2005; Liu et al., 2005a; Liu et al., 2005b; bound miRNAs. In plants, miRNAs cleave their regulated target mRNA, whereas in Meister et al., 2005; Pillai et al., 2005; Sen and Blau, 2005). mammals miRNAs promote translational repression of the targeted mRNA. Until recently, RNAi is a post-transcriptional silencing mechanism in which this was considered the major distinction between siRISC and miRISC in mammalian cells. However, new evidence suggests that miRNAs can also regulate mRNA degradation small double-stranded RNA molecules induce sequence-specific similarly to siRNAs (Bagga et al., 2005; Jing et al., 2005; Yekta et al., 2004), thus blurring degradation and/or translational repression of homologous the distinction between the two small-RNA-mediated silencing complexes. 1318 Journal of Cell Science 120 (8) GWBs are enriched in mRNA decay factors and pools of Segal et al., 2006). Furthermore, there are functional stored messenger ribonucleoproteins (mRNPs) (Bruno and differences between GWBs and yeast P-bodies in terms of their Wilkinson, 2006; Sheth and Parker, 2006). Moreover, they are responses to stress and cell growth (Schneider et al., 2006). For dynamic structures, whose size and number appear to depend example, P-bodies increase in size and number during growth on specific intracellular processes. For instance, GWBs vary in limitation, increased cell density, and stress (Teixeira et al., size and number throughout the cell cycle, the largest of which 2005), whereas GWBs increase in size and number in are observed in late S and G2 phase (Yang et al., 2004). proliferating cells (Yang et al., 2004) and dynamically interact Furthermore, stress (Kedersha et al., 2005; Teixeira et al., with stress granules‡ in stressed mammalian cells (Kedersha et 2005), cell proliferation (Yang et al., 2004), blocking mRNA al., 2005). Therefore, one needs to be cautious when decay (Andrei et al., 2005; Cougot et al., 2004; Sheth and generalizing about these structures because
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