Transcriptomics

Dataset Information

297

IFN-g Regulates mTORC1, Cellular Metabolism and mRNA Translation to Potentiate Inflammatory Macrophage Activation [RNA-Seq]


ABSTRACT: IFN-g primes macrophages for enhanced inflammatory activation by TLRs and microbial killing, but little is known about the regulation of cell metabolism or mRNA translation during priming. We found that IFN-g regulates macrophage metabolism and translation in an integrated manner by targeting mTORC1 and MNK pathways that converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of the central metabolic regulator mTORC1 by IFN-g was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages revealed that IFN-g selectively modulates the macrophage translatome to promote inflammation, further reprogram metabolic pathways, and modulate protein synthesis. These results add IFN-g-mediated metabolic reprogramming and translational regulation as key components of classical inflammatory macrophage activation. RPF and RNAseq libraries were generated from mock or IFN-g-primed human macrophages. Cells were stimulated with Pam3Cys and harvested at 4 hours. Libraries were generated using protocol modified from Illumina Truseq technology.

ORGANISM(S): Homo sapiens  

SUBMITTER: Gunnar Rätsch   Eugenia G Giannopoulou  Lionel B Ivashkiv  Xiaoyu Hu  Xiaodi Su  Yingpu Yu  Hui Liu  Justin R Cross  Yi Zhong  Charles M Rice 

PROVIDER: E-GEOD-66809 | ArrayExpress | 2015-06-29

SECONDARY ACCESSION(S): SRP056098GSE66809PRJNA278009

REPOSITORIES: GEO, ArrayExpress, ENA

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