P-Bodies React to Stress and Nonsense

Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
Cell (Impact Factor: 33.12). 07/2006; 125(6):1036-8. DOI: 10.1016/j.cell.2006.06.003
Source: PubMed

ABSTRACT P-bodies are specialized cytoplasmic compartments where translational repression and mRNA turnover may occur. Findings in this issue of Cell provide evidence that P-bodies are sites of "mRNA purgatory." Bhattacharyya et al. (2006) reveal that normal mRNA can be released from P-bodies and translated into protein in response to stress. Meanwhile, Sheth and Parker (2006) report that aberrant mRNAs are targeted to P-bodies to undergo rapid decay.

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    • "P-bodies contain translation repressors, mRNA degradation enzymes, and cofactors such as decapping holoenzyme and XRN1 exoribonuclease (Franks and Lykke-Andersen, 2008; Parker and Sheth, 2007), while SGs contain translation initiation machinery components (Anderson and Kedersha, 2008). Contrary to SGs, a limited number of p-bodies can be detected in cells under normal conditions , but both granule types increase in size and number upon stress-limiting translation initiation, such as heat (Bruno and Wilkinson, 2006; Weber et al., 2008). Although the mRNA decay machinery concentrates in p-bodies, it is still debated whether they are actual sites of mRNA decapping and degradation . "
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    • "Distinct classes of ribonucleoprotein (RNP) granules appear to function in specific aspects of RNA metabolism (Anderson and Kedersha, 2006). Cytoplasmic processing bodies, termed P bodies, are involved in mRNA degradation, nonsense-mediated RNA decay (NMD), siRNA-and micro- RNA (miRNA)-mediated gene silencing in mammalian cells (Sheth and Parker, 2003; Cougot et al., 2004; Jakymiw et al., 2005; Liu et al., 2005a, 2005b; Sen and Blau, 2005; Bruno and Wilkinson, 2006; Parker and Sheth, 2007). Consistently, P bodies contain components involved in 5' to 3' mRNA degradation, including the decapping complex DCAP1/ DCAP2, decapping coactivators (e.g. "
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    ABSTRACT: Cytoplasmic processing bodies, termed P bodies, are involved in diverse post-transcriptional processes including mRNA decay, nonsense-mediated RNA decay (NMD), RNAi, miRNA-mediated translational repression and storage of translationally silenced mRNAs. Regulation of the formation of P bodies in the context of multicellular organisms is poorly understood. Here we describe a systematic RNAi screen in C. elegans that identified 224 genes with diverse cellular functions whose inactivations result in a dramatic increase in the number of P bodies. 83 of these genes form a complex functional interaction network regulating NMD. We demonstrate that NMD interfaces with many cellular processes including translation, ubiquitin-mediated protein degradation, intracellular trafficking and cytoskeleton structure.We also uncover an extensive link between translation and RNAi, with different steps in protein synthesis appearing to have distinct effects on RNAi efficiency. Moreover, the intracellular vesicular trafficking network plays an important role in the regulation of RNAi. A subset of genes enhancing P body formation also regulate the formation of stress granules in C. elegans. Our study offers insights into the cellular mechanisms that regulate the formation of P bodies and also provides a framework for system-level understanding of NMD and RNAi in the context of the development of multicellular organisms.
    Protein & Cell 11/2011; 2(11):918-39. DOI:10.1007/s13238-011-1119-x · 2.85 Impact Factor
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    • "They consist of translation repressors, mRNA decapping proteins, and a 5–3 exonuclease. P-bodies are particularly important for translational repression during cellular stress, when repression of many mRNAs is crucial to halt growth and enhance cell survival (Bruno and Wilkinson, 2006; Sheth and Parker, 2006; Buchan et al., 2008; Gallo et al., 2008; Nissan and Parker, 2008). P-bodies are critical for the formation of stress granules, which are comprised of aggregates of untranslating mRNAs, a subset of translation initiation factors, the 40S ribosome subunit, and poly(A)-binding proteins, such as Pab1 and Pub1 (Anderson and Kedersha, 2008, 2009; Buchan et al., 2008). "
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