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P23 acts as functional RBP in the macrophage inflammation response

Macrophages exert the primary cellular immune response. Pathogen components like bacterial lipopolysaccharides (LPS) stimulate macrophage migration, phagocytotic activity and cytokine expression. Previously, we identified the poly(A)+ RNA interactome of RAW 264.7 macrophages. Of the 402 RNA-binding...

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Main Authors: Vries, Sebastian de (Author) , Benes, Vladimir (Author) , Naarmann-de Vries, Isabel S. (Author) , Rücklé, Cornelia (Author) , Zarnack, Katharina (Author) , Marx, Gernot (Author) , Ostareck, Dirk H. (Author) , Ostareck-Lederer, Antje (Author)
Format: Article (Journal)
Language:English
Published: 11 June 2021
In: Frontiers in molecular biosciences
Year: 2021, Volume: 8, Pages: 1-16
ISSN:2296-889X
DOI:10.3389/fmolb.2021.625608
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3389/fmolb.2021.625608
Verlag, lizenzpflichtig, Volltext: https://www.frontiersin.org/article/10.3389/fmolb.2021.625608
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Author Notes:Sebastian de Vries, Vladimir Benes, Isabel S. Naarmann-de Vries, Cornelia Rücklé, Katharina Zarnack, Gernot Marx, Dirk H. Ostareck and Antje Ostareck-Lederer
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Summary:Macrophages exert the primary cellular immune response. Pathogen components like bacterial lipopolysaccharides (LPS) stimulate macrophage migration, phagocytotic activity and cytokine expression. Previously, we identified the poly(A)+ RNA interactome of RAW 264.7 macrophages. Of the 402 RNA-binding proteins (RBPs), 32 were classified as unique in macrophages, including nineteen not reported to interact with nucleic acids before. Remarkably, P23 a HSP90 co-chaperone, also known as cytosolic prostaglandin E2 synthase (PTGES3), exhibited differential poly(A)+ RNA binding in untreated and LPS-induced macrophages. To identify mRNAs bound by P23 and to elucidate potential regulatory RBP functions in macrophages, we immunoprecipitated P23 from cytoplasmic extracts of cross-linked untreated and LPS-induced cells. RNAseq revealed that enrichment of 44 mRNAs was reduced in response to LPS. Kif15 mRNA, which encodes kinesin family member 15 (KIF15), a motor protein implicated in cytoskeletal reorganization and cell mobility was selected for further analysis. Noteworthy, phagocytic activity of LPS-induced macrophages was enhanced by P23 depletion. Specifically, in untreated RAW 264.7 macrophages, decreased P23 results in Kif15 mRNA destabilization, diminished KIF15 expression and accelerated macrophage migration. We show that the unexpected RBP function of P23 contributes to the regulation of macrophage phagocytotic activity and migration.
Item Description:Gesehen am 13.08.2021
Physical Description:Online Resource
ISSN:2296-889X
DOI:10.3389/fmolb.2021.625608

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