Andrei, M. A. et al. A role for eIF4E and eIF4E-transporter in targeting mRNPs to mammalian processing bodies. RNA 11, 717-727

Department of Cellular Biochemistry, Max-Planck-Institute of Biophysical Chemistry, D-37077 Göttingen, Germany.
RNA (Impact Factor: 4.94). 05/2005; 11(5):717-27. DOI: 10.1261/rna.2340405
Source: PubMed

ABSTRACT mRNP remodeling events required for the transition of an mRNA from active translation to degradation are currently poorly understood. We identified protein factors potentially involved in this transition, which are present in mammalian P bodies, cytoplasmic foci enriched in 5' --> 3' mRNA degrading enzymes. We demonstrate that human P bodies contain the cap-binding protein eIF4E and the related factor eIF4E-transporter (eIF4E-T), suggesting novel roles for these proteins in targeting mRNAs for 5' --> 3' degradation. Furthermore, fluorescence resonance energy transfer (FRET) studies indicate that eIF4E interacts with eIF4E-T and the putative DEAD box helicase rck/p54 in the P bodies in vivo. RNAi-mediated knockdowns revealed that a subset of P body factors, including eIF4E-T, LSm1, rck/p54, and Ccr4 are required for the accumulation of each other and eIF4E in P bodies. In addition, treatment of HeLa cells with cycloheximide, which inhibits translation, revealed that mRNA is also required for accumulation of mRNA degradation factors in P bodies. In contrast, knockdown of the decapping enzyme Dcp2, which initiates the actual 5' --> 3' mRNA degradation did not abolish P body formation, indicating it first functions after mRNPs have been targeted to these cytoplasmic foci. These data support a model in which mRNPs undergo several successive steps of remodeling and/or 3' trimming until their composition or structural organization promotes their accumulation in P bodies.

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    • "It has also been reported that mRNA is required for cytoplasmic P-body maintenance (Cougot et al., 2004; Andrei et al., 2005; Ferraiuolo et al., 2005). Furthermore, a recent study showed that after nocodazole treatment, HIF-1a mRNA, which is overexpressed in solid tumors, accumulates in Pbodies . "
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    ABSTRACT: Metastatic Lymph Node 51 (MLN51) is a core component of the exon junction complex (EJC), which is loaded on spliced mRNAs and plays an essential role in their fate. Unlike the three other EJC core components (eIF4AIII, Magoh and Y14), MLN51 is mainly located in the cytoplasm where it plays a key role in stress granules assembly. In this study, we further investigated the cytoplasmic role of MLN51. We show that MLN51 is a new component of processing bodies (P-bodies). When overexpressed, MLN51 localizes in novel small cytoplasmic foci. These contain RNA, show directed movements, and are distinct from stress granules and P-bodies. The appearance of these foci correlates with the process of P-body disassembly. A similar reduction in PB count is also observed in human HER2+ breast cancer cells overexpressing MLN51. This suggests that P-body disassembly and subsequent mRNA deregulation may correlate to cancer progression.
    Journal of Cell Science 09/2014; 127(21). DOI:10.1242/jcs.154500 · 5.43 Impact Factor
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    • "Similar enhanced formation of DCAP-1::GFP granules was observed in response to oxidative stress induced by sodium arsenite (BRF155, Fig. S2A). We further showed that RNAi-mediated knockdown of a core PB component, cgh-1 (encoding a conserved DEAD-box RNA helicase) was sufficient to disrupt the formation of DCAP-1::GFP granules during heat (Fig. 2C, D) or oxidative stress (data not shown), in agreement with studies in yeast or human cells [8], [56]. "
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    ABSTRACT: Processing bodies (PBs) and stress granules (SGs) are related, cytoplasmic RNA-protein complexes that contribute to post-transcriptional gene regulation in all eukaryotic cells. Both structures contain translationally repressed mRNAs and several proteins involved in silencing, stabilization or degradation of mRNAs, especially under environmental stress. Here, we monitored the dynamic formation of PBs and SGs, in somatic cells of adult worms, using fluorescently tagged protein markers of each complex. Both complexes were accumulated in response to various stress conditions, but distinct modes of SG formation were induced, depending on the insult. We also observed an age-dependent accumulation of PBs but not of SGs. We further showed that direct alterations in PB-related genes can influence aging and normal stress responses, beyond their developmental role. In addition, disruption of SG-related genes had diverse effects on development, fertility, lifespan and stress resistance of worms. Our work therefore underlines the important roles of mRNA metabolism factors in several vital cellular processes and provides insight into their diverse functions in a multicellular organism.
    PLoS ONE 07/2014; 9(7):e103365. DOI:10.1371/journal.pone.0103365 · 3.23 Impact Factor
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    • "Decapping activity is prevented by the translation initiation factor eIF4E, a 5 cap-binding protein (von der Haar et al., 2004). Its localization in PB and SG is documented in humans and yeast (Andrei et al., 2005; Brengues and Parker, 2007), but the homolog of Arabidopsis was only detected in SG (Weber et al., 2008). "
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    ABSTRACT: mRNA accumulation is tightly regulated by diverse molecular pathways. The identification and characterization of enzymes and regulatory proteins involved in controlling the fate of mRNA offers the possibility to broaden our understanding of posttranscriptional gene regulation. Processing bodies (P bodies, PB) are cytoplasmic protein complexes involved in degradation and translational arrest of mRNA. Composition and dynamics of these subcellular structures have been studied in animal systems, yeasts and in the model plant Arabidopsis. Their assembly implies the aggregation of specific factors related to decapping, deadenylation, and exoribonucleases that operate synchronously to regulate certain mRNA targets during development and adaptation to stress. Although the general function of PB along with the flow of genetic information is understood, several questions still remain open. This review summarizes data on the composition, potential molecular roles, and biological significance of PB and potentially related proteins in Arabidopsis.
    Frontiers in Plant Science 05/2014; 5:201. DOI:10.3389/fpls.2014.00201 · 3.95 Impact Factor
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