Luo et al. 2023 (PRJNA934078)

Title	METTL3 mediated m6A mRNA methylation regulates neutrophil activation through targeting TLR4 signaling (Ribosome-Seq)
Organism
Number of Samples	4
Release Date	2023/02/12 00:00
Sequencing Types
Protocol Details

GWIPS-viz	Trips-Viz

Title
Authors	Luo S,Liao C,Zhang L,Ling C,Zhang X,Xie P,Su G,Chen Z,Zhang L,Lai T,Tang J
Journal	Cell reports
Publication Date	2023 Mar 28
Abstract	N6-methyladenosine (m6A) modification accounts for the most prevalent mRNA internal modification and has emerged as a widespread regulatory mechanism in multiple physiological processes. We address a role of methyltransferase-like protein 3 (METTL3) in neutrophil activation. METTL3 controls neutrophil release from bone marrow to circulation through surface expression of CXC chemokine receptor 2 (CXCR2) in a Toll-like receptor 4 (TLR4) signaling-dependent manner in lipopolysaccharide (LPS)-induced endotoxemia. We show that the mRNA of TLR4 is modified by m6A, exhibiting increased translation and slowed degradation simultaneously, leading to elevated protein levels of TLR4, which eventually promotes the TLR4 signaling activation of neutrophil. The reduced expression of TLR4 lowers cytokine secretion in METTL3-deleted neutrophils upon LPS stimulation through TLR4/Myd88/nuclear factor κB (NF-κB) signaling. Collectively, these data demonstrate that METTL3 modulation of TLR4 expression is a critical determinant of neutrophil activation in endotoxemia. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
PMC
PMID	36920907
DOI

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