P-Bodies React to Stress and Nonsense
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 . "
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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- "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. "
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). "
ABSTRACT: The mRNA-binding protein Ssd1 is a substrate for the Saccharomyces cerevisiae LATS/NDR orthologue Cbk1, which controls polarized growth, cell separation, and cell integrity. We discovered that most Ssd1 localizes diffusely within the cytoplasm, but some transiently accumulates at sites of polarized growth. Cbk1 inhibition and cellular stress cause Ssd1 to redistribute to mRNA processing bodies (P-bodies) and stress granules, which are known to repress translation. Ssd1 recruitment to P-bodies is independent of mRNA binding and is promoted by the removal of Cbk1 phosphorylation sites. SSD1 deletion severely impairs the asymmetric localization of the Ssd1-associated mRNA, SRL1. Expression of phosphomimetic Ssd1 promotes polarized localization of SRL1 mRNA, whereas phosphorylation-deficient Ssd1 causes constitutive localization of SRL1 mRNA to P-bodies and causes cellular lysis. These data support the model that Cbk1-mediated phosphorylation of Ssd1 promotes the cortical localization of Ssd1-mRNA complexes, whereas Cbk1 inhibition, cellular stress, and Ssd1 dephosphorylation promote Ssd1-mRNA interactions with P-bodies and stress granules, leading to translational repression.The Journal of Cell Biology 02/2011; 192(4):583-98. DOI:10.1083/jcb.201011061 · 9.69 Impact Factor