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      Stress-dependent relocalization of translationally primed mRNPs to cytoplasmic granules that are kinetically and spatially distinct from P-bodies

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          Abstract

          Cytoplasmic RNA granules serve key functions in the control of messenger RNA (mRNA) fate in eukaryotic cells. For instance, in yeast, severe stress induces mRNA relocalization to sites of degradation or storage called processing bodies (P-bodies). In this study, we show that the translation repression associated with glucose starvation causes the key translational mediators of mRNA recognition, eIF4E, eIF4G, and Pab1p, to resediment away from ribosomal fractions. These mediators then accumulate in P-bodies and in previously unrecognized cytoplasmic bodies, which we define as EGP-bodies. Our kinetic studies highlight the fundamental difference between EGP- and P-bodies and reflect the complex dynamics surrounding reconfiguration of the mRNA pool under stress conditions. An absence of key mRNA decay factors from EGP-bodies points toward an mRNA storage function for these bodies. Overall, this study highlights new potential control points in both the regulation of mRNA fate and the global control of translation initiation.

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          Most cited references28

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          P bodies and the control of mRNA translation and degradation.

          Recent results indicate that many untranslating mRNAs in somatic eukaryotic cells assemble into related mRNPs that accumulate in specific cytoplasmic foci referred to as P bodies. Transcripts associated with P body components can either be degraded or return to translation. Moreover, P bodies are also biochemically and functionally related to some maternal and neuronal mRNA granules. This suggests an emerging model of cytoplasmic mRNA function in which the rates of translation and degradation of mRNAs are influenced by a dynamic equilibrium between polysomes and the mRNPs seen in P bodies. Moreover, some mRNA-specific regulatory factors, including miRNAs and RISC, appear to repress translation and promote decay by recruiting P body components to individual mRNAs.
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            RNA granules

            Cytoplasmic RNA granules in germ cells (polar and germinal granules), somatic cells (stress granules and processing bodies), and neurons (neuronal granules) have emerged as important players in the posttranscriptional regulation of gene expression. RNA granules contain various ribosomal subunits, translation factors, decay enzymes, helicases, scaffold proteins, and RNA-binding proteins, and they control the localization, stability, and translation of their RNA cargo. We review the relationship between different classes of these granules and discuss how spatial organization regulates messenger RNA translation/decay.
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              Regulation of cap-dependent translation by eIF4E inhibitory proteins.

              Eukaryotic messenger RNAs contain a modified guanosine, termed a cap, at their 5' ends. Translation of mRNAs requires the binding of an initiation factor, eIF4E, to the cap structure. Here, we describe a family of proteins that through a shared sequence regulate cap-dependent translation. The biological importance of this translational regulation is immense, and affects such processes as cell growth, development, oncogenic transformation and perhaps even axon pathfinding and memory consolidation.
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                Author and article information

                Journal
                J Cell Biol
                jcb
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                8 October 2007
                : 179
                : 1
                : 65-74
                Affiliations
                Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK
                Author notes

                Correspondence to Mark P. Ashe: mark.p.ashe@ 123456manchester.ac.uk

                Article
                200707010
                10.1083/jcb.200707010
                2064737
                17908917
                c6050ee1-5de2-49ec-b872-c46f45feb2a6
                Copyright © 2007, The Rockefeller University Press
                History
                : 2 July 2007
                : 6 September 2007
                Categories
                Research Articles
                Article

                Cell biology
                Cell biology

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