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 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.
Author:Sebastian de Vries, Vladimir Benes, Isabel S. Naarmann-de Vries, Cornelia Rücklé, Katharina ZarnackORCiDGND, Gernot Marx, Dirk H. Ostareck, Antje Ostareck-Lederer
Parent Title (English):Frontiers in molecular biosciences
Place of publication:Lausanne
Document Type:Article
Date of Publication (online):2021/06/11
Date of first Publication:2021/06/11
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/07/05
Tag:Kif15 mRNA; P23/PTGES3; RNA-binding protein; macrophage inflammatory response; migration; phagocytosis; post-transcriptional control of gene expression
Issue:art. 625608
Page Number:16
First Page:1
Last Page:16
Institutes:Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe
Fachübergreifende Einrichtungen / Buchmann Institut für Molekulare Lebenswissenschaften (BMLS)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0