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      Stress Granules and Processing Bodies in Translational Control

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      Cold Spring Harbor Perspectives in Biology
      Cold Spring Harbor Laboratory

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          Abstract

          Stress granules (SGs) and processing bodies (PBs) are non-membrane-enclosed RNA granules that dynamically sequester translationally inactive messenger ribonucleoprotein particles (mRNPs) into compartments that are distinct from the surrounding cytoplasm. mRNP remodeling, silencing, and/or storage involves the dynamic partitioning of closed-loop polyadenylated mRNPs into SGs, or the sequestration of deadenylated, linear mRNPs into PBs. SGs form when stress-activated pathways stall translation initiation but allow elongation and termination to occur normally, resulting in a sudden excess of mRNPs that are spatially condensed into discrete foci by protein:protein, protein:RNA, and RNA:RNA interactions. In contrast, PBs can exist in the absence of stress, when specific factors promote mRNA deadenylation, condensation, and sequestration from the translational machinery. The formation and dissolution of SGs and PBs reflect changes in messenger RNA (mRNA) metabolism and allow cells to modulate the proteome and/or mediate life or death decisions during changing environmental conditions.

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          Most cited references72

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          Stress granules: the Tao of RNA triage.

          Cytoplasmic RNA structures such as stress granules (SGs) and processing bodies (PBs) are functional byproducts of mRNA metabolism, sharing substrate mRNA, dynamic properties and many proteins, but also housing separate components and performing independent functions. Each can exist independently, but when coordinately induced they are often tethered together in a cytosolic dance. Although both self-assemble in response to stress-induced perturbations in translation, several recent reports reveal novel proteins and RNAs that are components of these structures but also perform other cellular functions. Proteins that mediate splicing, transcription, adhesion, signaling and development are all integrated with SG and PB assembly. Thus, these ephemeral bodies represent more than just the dynamic sorting of mRNA between translation and decay.
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            Cell-free formation of RNA granules: bound RNAs identify features and components of cellular assemblies.

            Cellular granules lacking boundary membranes harbor RNAs and their associated proteins and play diverse roles controlling the timing and location of protein synthesis. Formation of such granules was emulated by treatment of mouse brain extracts and human cell lysates with a biotinylated isoxazole (b-isox) chemical. Deep sequencing of the associated RNAs revealed an enrichment for mRNAs known to be recruited to neuronal granules used for dendritic transport and localized translation at synapses. Precipitated mRNAs contain extended 3' UTR sequences and an enrichment in binding sites for known granule-associated proteins. Hydrogels composed of the low complexity (LC) sequence domain of FUS recruited and retained the same mRNAs as were selectively precipitated by the b-isox chemical. Phosphorylation of the LC domain of FUS prevented hydrogel retention, offering a conceptual means of dynamic, signal-dependent control of RNA granule assembly. Copyright © 2012 Elsevier Inc. All rights reserved.
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              N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis

              A comprehensive proteomics screen for ‘reader’ proteins that recognize m6A-modified RNA reveals that the modification both promotes and prevents the binding of factors that control mRNA homeostasis in mammalian cells.
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                Author and article information

                Journal
                Cold Spring Harbor Perspectives in Biology
                Cold Spring Harb Perspect Biol
                Cold Spring Harbor Laboratory
                1943-0264
                May 01 2019
                May 2019
                May 2019
                August 06 2018
                : 11
                : 5
                : a032813
                Article
                10.1101/cshperspect.a032813
                6496347
                30082464
                3265aa3b-5539-47e7-b452-1dcbd9a331e4
                © 2018
                History

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