P23 Acts as Functional RBP in the Macrophage Inflammation Response

Author:

de Vries Sebastian,Benes Vladimir,Naarmann-de Vries Isabel S.,Rücklé Cornelia,Zarnack Katharina,Marx Gernot,Ostareck Dirk H.,Ostareck-Lederer Antje

Abstract

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.

Funder

Deutsche Forschungsgemeinschaft

Publisher

Frontiers Media SA

Subject

Biochemistry, Genetics and Molecular Biology (miscellaneous),Molecular Biology,Biochemistry

Reference85 articles.

1. HTSeq–a Python Framework to Work with High-Throughput Sequencing Data;Anders;Bioinformatics,2015

2. Fitting a Mixture Model by Expectation Maximization to Discover Motifs in Biopolymers;Bailey;Proc. Int. Conf. Intell. Syst. Mol. Biol.,1994

3. MEME SUITE: Tools for Motif Discovery and Searching;Bailey;Nucleic Acids Res.,2009

4. Combining Evidence Using P-Values: Application to Sequence Homology Searches;Bailey;Bioinformatics,1998

5. The mRNA-Bound Proteome and its Global Occupancy Profile on Protein-Coding Transcripts;Baltz;Mol. Cel,2012

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3