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      Protein Methylation and Stress Granules: Posttranslational Remodeler or Innocent Bystander?

      review-article
      1 , 2 , *
      Molecular Biology International
      SAGE-Hindawi Access to Research

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          Abstract

          Stress granules contain a large number of post-translationally modified proteins, and studies have shown that these modifications serve as recruitment tags for specific proteins and even control the assembly and disassembly of the granules themselves. Work originating from our laboratory has focused on the role protein methylation plays in stress granule composition and function. We have demonstrated that both asymmetrically and symmetrically dimethylated proteins are core constituents of stress granules, and we have endeavored to understand when and how this occurs. Here we seek to integrate this data into a framework consisting of the currently known post-translational modifications affecting stress granules to produce a model of stress granule dynamics that, in turn, may serve as a benchmark for understanding and predicting how post-translational modifications regulate other granule types.

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          Most cited references64

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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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            Dynamic Shuttling of Tia-1 Accompanies the Recruitment of mRNA to Mammalian Stress Granules

            Mammalian stress granules (SGs) harbor untranslated mRNAs that accumulate in cells exposed to environmental stress. Drugs that stabilize polysomes (emetine) inhibit the assembly of SGs, whereas drugs that destabilize polysomes (puromycin) promote the assembly of SGs. Moreover, emetine dissolves preformed SGs as it promotes the assembly of polysomes, suggesting that these mRNP species (i.e., SGs and polysomes) exist in equilibrium. We used green flourescent protein–tagged SG-associated RNA-binding proteins (specifically, TIA-1 and poly[A] binding protein [PABP-I]) to monitor SG assembly, disassembly, and turnover in live cells. Fluorescence recovery after photobleaching shows that both TIA-1 and PABP-I rapidly and continuously shuttle in and out of SGs, indicating that the assembly of SGs is a highly dynamic process. This unexpected result leads us to propose that mammalian SGs are sites at which untranslated mRNAs are sorted and processed for either reinitiation, degradation, or packaging into stable nonpolysomal mRNP complexes. A truncation mutant of TIA-1 (TIA-1ΔRRM), which acts as a transdominant inhibitor of SG assembly, promotes the expression of cotransfected reporter genes in COS transfectants, suggesting that this process of mRNA triage might, directly or indirectly, influence protein expression.
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              Stressful initiations.

              Stress granules (SGs) are phase-dense particles that appear in the cytoplasm of eukaryotic cells that have been exposed to environmental stress (e.g. heat, oxidative conditions, hyperosmolarity and UV irradiation). SG assembly is a consequence of abortive translational initiation: SGs appear when translation is initiated in the absence of eIF2-GTP-tRNA(i)(Met), the ternary complex that normally loads tRNA(i)(Met) onto the small ribosomal subunit. Stress-induced depletion of eIF2-GTP-tRNA(i)(Met) allows the related RNA-binding proteins TIA-1 and TIAR to promote the assembly of eIF2-eIF5-deficient preinitiation complexes, the core constituents of SGs. The mRNP components that make up the SG are in a dynamic equilibrium with polysomes. As such, the SG appears to constitute a metabolic domain through which mRNPs are continually routed and subjected to triage - they are first monitored for integrity and composition, and then sorted for productive translational initiation or targeted degradation.
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                Author and article information

                Journal
                Mol Biol Int
                MBI
                Molecular Biology International
                SAGE-Hindawi Access to Research
                2090-2182
                2090-2190
                2011
                24 February 2011
                : 2011
                : 137459
                Affiliations
                1Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 1065, USA
                2Biochemical Molecular Neurobiology Laboratory, Department of Molecular Biology, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
                Author notes
                *Robert B. Denman: rbdenman@ 123456yahoo.com

                Academic Editor: Jörg Kobarg

                Article
                10.4061/2011/137459
                3196864
                22091395
                8d6d1d43-1c06-4fb4-9497-ba84aec4477d
                Copyright © 2011 W. Xie and R. B. Denman.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 November 2010
                : 10 January 2011
                Categories
                Review Article

                Molecular biology
                Molecular biology

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