Viral Manipulation of a Mechanoresponsive Signaling Axis Disassembles Processing Bodies.

Published on Sep 13, 2021in Molecular and Cellular Biology4.272
· DOI :10.1128/MCB.00399-21
Elizabeth L. Castle2
Estimated H-index: 2
(Dal: Dalhousie University),
Carolyn-Ann Robinson1
Estimated H-index: 1
(U of C: University of Calgary)
+ 2 AuthorsJennifer A. Corcoran15
Estimated H-index: 15
(U of C: University of Calgary)
Sources
Abstract
Processing bodies (PBs) are ribonucleoprotein granules important for cytokine mRNA decay that are targeted for disassembly by many viruses. Kaposi's sarcoma-associated herpesvirus is the etiological agent of the inflammatory endothelial cancer, Kaposi's sarcoma, and a PB-regulating virus. The virus encodes kaposin B (KapB), which induces actin stress fibers (SFs) and cell spindling as well as PB disassembly. We now show that KapB-mediated PB disassembly requires actin rearrangements, RhoA effectors, and the mechanoresponsive transcription activator, YAP. Moreover, ectopic expression of active YAP or exposure of ECs to mechanical forces caused PB disassembly in the absence of KapB. We propose that the viral protein KapB activates a mechanoresponsive signaling axis and links changes in cell shape and cytoskeletal structures to enhanced inflammatory molecule expression using PB disassembly. Our work implies that cytoskeletal changes in other pathologies may similarly impact the inflammatory environment.
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References141
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#1Carolyn-Ann Robinson (Dal: Dalhousie University)H-Index: 3
#2Gillian K. Singh (Dal: Dalhousie University)H-Index: 2
Last. Jennifer A. Corcoran (U of C: University of Calgary)H-Index: 15
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Selective autophagy receptors contribute to host defence by targeting intracellular microbes for degradation and fine-tuning inflammatory processes by directing the degradation of macromolecular immune signaling platforms. Processing bodies (PBs) are cytoplasmic ribonucleoprotein granules that control inflammation by silencing and/or degrading labile messenger RNAs (mRNAs) that encode inflammatory mediator proteins. PBs often disassemble in response to virus infection, which correlates with incr...
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#1Masahiro Kimura (Kyoto University)H-Index: 13
#2Takahiro Horie (Kyoto University)H-Index: 19
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The Hippo signaling pathway is involved in the pathophysiology of various cardiovascular diseases. Yes-associated protein (YAP) and transcriptional enhancer activator domain (TEAD) transcriptional factors, the main transcriptional complex of the Hippo pathway, were recently identified as modulators of phenotypic switching of vascular smooth muscle cells (VSMCs). However, the intrinsic regulator of YAP/TEAD-mediated gene expressions involved in vascular pathophysiology remains to be elucidated. H...
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Host nucleases are implicated in antiviral response through the processing of pathogen-derived nucleic acids. Among many host RNases, decapping enzymes DCP1 and 2, and 5′→3′ exonuclease XRN1, which are components of the RNA decay machinery, have been extensively studied in prokaryotes, plants, and invertebrates but less so in mammalian systems. As a result, the implication of XRN1 and DCPs in viral replication, in particular, the spatio-temporal dynamics during RNA viral infections remains elusi...
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#1Nishi R. SharmaH-Index: 8
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Cellular non-membranous RNA-granules, P-bodies (RNA processing bodies, PB) and stress granules (SG), are important components of the innate immune response to virus invasion. Mechanisms governing how a virus modulates PB formation remain elusive. Here, we report the important roles of GW182 and DDX6, but not Dicer, Ago2 and DCP1A, in PB formation, and that Kaposi’s sarcoma-associated herpesvirus (KSHV) lytic infection reduces PB formation through several specific interactions with viral RNA-bind...
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Summary Biological phase transitions form membrane-less organelles that generate distinct cellular environments. How molecules are partitioned between these compartments and the surrounding cellular space and the functional consequence of this localization is not well understood. Here, we report the localization of mRNA to stress granules (SGs) and processing bodies (PBs) and its effect on translation and degradation during the integrated stress response. Using single mRNA imaging in living huma...
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This study was supported by the Ministerio de Ciencia, Innovacion y Universidades (grants SAF2011-25047, CSD2009-0016, SAF2014-51876-R, and SAF2017-83130-R and IGP-SO grant MINSEV1512-07-2016), the European Regional Development Fund (ERDF ``A way to make Europe''), Fundacio la Marato de TV3 (grant 674/C/2013), and Worldwide Cancer Research (grant 15-0404) (all to M.A.d.P.). R.M.-V. was supported by Ministerio de Ciencia, Innovacion y Universidades (predoctoral fellowship BES-2012-052980; FPI, SA...
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