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      RNA-binding proteins as a point of convergence of the PI3K and p38 MAPK pathways

      research-article
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      Frontiers in Immunology
      Frontiers Media S.A.
      RNA-binding proteins, PI3K, MAPK

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          Abstract

          Understanding the mechanisms by which signal transduction pathways mediate changes in RNA abundance requires the examination of the fate of RNA from its transcription to its degradation. Evidence suggests that RNA abundance is partly regulated by post-transcriptional mechanisms affecting RNA decay and this in turn is modulated by some of the same signaling pathways that control transcription. Furthermore, the translation of mRNA is a key regulatory step that is influenced by signal transduction. These processes are regulated, in part, by RNA-binding proteins (RBPs) which bind to sequence-specific RNA elements. The function of RBPs is controlled and co-ordinated by phosphorylation. Based on the current literature we hypothesize that RBPs may be a point of convergence for the activity of different kinases such as phosphoinositide-3-kinase and mitogen-activated protein kinase which regulate RBP localization and function.

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          Most cited references70

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          RNA regulons: coordination of post-transcriptional events.

          Jack Keene (2007)
          Recent findings demonstrate that multiple mRNAs are co-regulated by one or more sequence-specific RNA-binding proteins that orchestrate their splicing, export, stability, localization and translation. These and other observations have given rise to a model in which mRNAs that encode functionally related proteins are coordinately regulated during cell growth and differentiation as post-transcriptional RNA operons or regulons, through a ribonucleoprotein-driven mechanism. Here I describe several recently discovered examples of RNA operons in budding yeast, fruitfly and mammalian cells, and their potential importance in processes such as immune response, oxidative metabolism, stress response, circadian rhythms and disease. I close by considering the evolutionary wiring and rewiring of these combinatorial post-transcriptional gene-expression networks.
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            The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC.

            Since their discovery almost two decades ago, microRNAs (miRNAs) have been shown to function by post-transcriptionally regulating protein accumulation. Understanding how miRNAs silence targeted mRNAs has been the focus of intensive research. Multiple models have been proposed, with few mechanistic details having been worked out. However, the past few years have witnessed a quantum leap forward in our understanding of the molecular mechanics of miRNA-mediated gene silencing. In this review we describe recent discoveries, with an emphasis on how miRISC post-transcriptionally controls gene expression by inhibiting translation and/or initiating mRNA decay, and how trans-acting factors control miRNA action.
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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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                Author and article information

                Journal
                Front Immunol
                Front Immunol
                Front. Immun.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                26 December 2012
                2012
                : 3
                : 398
                Affiliations
                Laboratory of Lymphocyte Signalling and Development, The Babraham Institute Babraham, UK
                Author notes

                Edited by: Klaus Okkenhaug, Babraham Institute, UK

                Reviewed by: Dinesh S. Rao, University of California, Los Angeles, USA; Roberto Gherzi, Istituto Nazionale per la Ricerca sul Cancro, Italy

                *Correspondence: Ram K. C. Venigalla and Martin Turner, Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Babraham CB22 3AT, UK. e-mail: ramkumar.venigalla@ 123456babraham.ac.uk ; martin.turner@ 123456babraham.ac.uk

                This article was submitted to Frontiers in B Cell Biology, a specialty of Frontiers in Immunology.

                Article
                10.3389/fimmu.2012.00398
                3530045
                23272005
                23c677ca-0897-4468-8119-6f708e6d880f
                Copyright © Venigalla and Turner.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 02 July 2012
                : 10 December 2012
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 93, Pages: 9, Words: 0
                Categories
                Immunology
                Review Article

                Immunology
                rna-binding proteins,pi3k,mapk
                Immunology
                rna-binding proteins, pi3k, mapk

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