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: 32.24). 07/2006; 125(6):1036-8. DOI: 10.1016/j.cell.2006.06.003
Source: PubMed


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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    ABSTRACT: To survive adverse and ever-changing environmental conditions, an organism must be able to adapt. It has long been established that the cellular reaction to stress includes the upregulation of genes coding for specific stress-responsive factors. In the present study, we demonstrate that during the early steps of the heat stress response, 25% of the Arabidopsis seedling transcriptome is targeted for rapid degradation. Our findings demonstrate that this process is catalyzed from 5' to 3' by the cytoplasmic exoribonuclease XRN4, whose function is seemingly reprogrammed by the heat-sensing pathway. The bulk of mRNAs subject to heat-dependent degradation are likely to include both the ribosome-released and polysome associated polyadenylated pools. The cotranslational decay process is facilitated at least in part by LARP1, a heat-specific cofactor of XRN4 required for its targeting to polysomes. Commensurate with their respective involvement at the molecular level, LARP1 and XRN4 are necessary for the thermotolerance of plants to long exposure to moderately high temperature, with xrn4 null mutants being almost unable to survive. These findings provide mechanistic insights regarding a massive stress-induced posttranscriptional downregulation and outline a potentially crucial pathway for plant survival and acclimation to heat stress.
    Cell Reports 12/2013; 5(5):1279-1293. DOI:10.1016/j.celrep.2013.11.019 · 8.36 Impact Factor
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    • "Furthermore, PBs co-localize with stress granules (SGs), suggesting that they probably interact with each other and function together in stress responses[19-21]. The significant increase of PBs in response to stress and their close connection with SGs indicate that mRNA decay, especially the decapping pathway, plays an important role in cellular stress responses[22,23]. However, little information is available for a complete view of mRNA degradation under stress conditions. "
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    ABSTRACT: mRNA degradation is a critical factor in determining mRNA abundance and enables rapid adjustment of gene expression in response to environmental stress. The involvement of processing bodies in stress response suggests a role for decapping-mediated mRNA degradation. However, little is known about the role of mRNA degradation under stressful environmental conditions. Here, we perform a global study of uncapped mRNAs, via parallel analysis of RNA ends (PARE), under cold stress in Brachypodium distachyon. Enrichment analysis indicates that degradation products detected by PARE are mainly generated by the decapping pathway. Endonucleolytic cleavages are detected, uncovering another way of modulating gene expression. PARE and RNA-seq analyses identify four types of mRNA decay patterns. Type II genes, for which light-harvesting processes are over-represented in gene ontology analyses, show unchanged transcript abundance and altered uncapped transcript abundance. Uncapping-mediated transcript stability of light harvesting-related genes changes significantly in response to cold stress, which may allow rapid adjustments in photosynthetic activity in response to cold stress. Transcript abundance and uncapped transcript abundance for type III genes changes in opposite directions in response to cold stress, indicating that uncapping-mediated mRNA degradation plays a role in regulating gene expression. To our knowledge, this is the first global analysis of mRNA degradation under environmental stress conditions in Brachypodium distachyon. We uncover specific degradation and endonucleolytic cleavage patterns under cold stress, which will deepen our understanding of mRNA degradation under stressful environmental conditions, as well as the cold stress response mechanism in monocots.
    Genome biology 08/2013; 14(8):R92. DOI:10.1186/gb-2013-14-8-r92 · 10.81 Impact Factor
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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 · 3.25 Impact Factor
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