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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-bindin...

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Autores principales: de Vries, Sebastian, Benes, Vladimir, Naarmann-de Vries, Isabel S., Rücklé, Cornelia, Zarnack, Katharina, Marx, Gernot, Ostareck, Dirk H., Ostareck-Lederer, Antje
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226254/
https://www.ncbi.nlm.nih.gov/pubmed/34179071
http://dx.doi.org/10.3389/fmolb.2021.625608
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author de Vries, Sebastian
Benes, Vladimir
Naarmann-de Vries, Isabel S.
Rücklé, Cornelia
Zarnack, Katharina
Marx, Gernot
Ostareck, Dirk H.
Ostareck-Lederer, Antje
author_facet de Vries, Sebastian
Benes, Vladimir
Naarmann-de Vries, Isabel S.
Rücklé, Cornelia
Zarnack, Katharina
Marx, Gernot
Ostareck, Dirk H.
Ostareck-Lederer, Antje
author_sort de Vries, Sebastian
collection PubMed
description 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.
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spelling pubmed-82262542021-06-26 P23 Acts as Functional RBP in the Macrophage Inflammation Response de Vries, Sebastian Benes, Vladimir Naarmann-de Vries, Isabel S. Rücklé, Cornelia Zarnack, Katharina Marx, Gernot Ostareck, Dirk H. Ostareck-Lederer, Antje Front Mol Biosci Molecular Biosciences 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. Frontiers Media S.A. 2021-06-11 /pmc/articles/PMC8226254/ /pubmed/34179071 http://dx.doi.org/10.3389/fmolb.2021.625608 Text en Copyright © 2021 de Vries, Benes, Naarmann-de Vries, Rücklé, Zarnack, Marx, Ostareck and Ostareck-Lederer. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
de Vries, Sebastian
Benes, Vladimir
Naarmann-de Vries, Isabel S.
Rücklé, Cornelia
Zarnack, Katharina
Marx, Gernot
Ostareck, Dirk H.
Ostareck-Lederer, Antje
P23 Acts as Functional RBP in the Macrophage Inflammation Response
title P23 Acts as Functional RBP in the Macrophage Inflammation Response
title_full P23 Acts as Functional RBP in the Macrophage Inflammation Response
title_fullStr P23 Acts as Functional RBP in the Macrophage Inflammation Response
title_full_unstemmed P23 Acts as Functional RBP in the Macrophage Inflammation Response
title_short P23 Acts as Functional RBP in the Macrophage Inflammation Response
title_sort p23 acts as functional rbp in the macrophage inflammation response
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226254/
https://www.ncbi.nlm.nih.gov/pubmed/34179071
http://dx.doi.org/10.3389/fmolb.2021.625608
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