TY  - JOUR
A1  - Vries, Sebastian de
A1  - Benes, Vladimir
A1  - Naarmann-de Vries, Isabel S.
A1  - Rücklé, Cornelia
A1  - Zarnack, Katharina
A1  - Marx, Gernot
A1  - Ostareck, Dirk H.
A1  - Ostareck-Lederer, Antje
T1  - P23 acts as functional RBP in the macrophage inflammation response
T2  - Frontiers in molecular biosciences
N2  - 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.
KW  - macrophage inflammatory response
KW  - RNA-binding protein
KW  - P23/PTGES3
KW  - Kif15 mRNA
KW  - migration
KW  - phagocytosis
KW  - post-transcriptional control of gene expression
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/61404
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-614048
SN  - 2296-889X
VL  - 8
IS  - art. 625608
SP  - 1
EP  - 16
PB  - Frontiers
CY  - Lausanne
ER  -