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TitleDiverging mRNA and Protein Networks in Activated Microglia Reveal SRSF3 Suppresses Translation of Highly Upregulated Innate Immune Transcripts.
Publication TypeJournal Article
Year of Publication2017
AuthorsBoutej, Hejer, Reza Rahimian, Sai Sampath Thammisetty, Louis-Charles Béland, Mélanie Lalancette-Hébert, and Jasna Kriz
JournalCell Rep
Date Published2017 Dec 12
KeywordsAnimals, Binding Sites, Cerebral Cortex, Female, Gene Expression Profiling, Gene Expression Regulation, Gene Regulatory Networks, Immunity, Innate, Lipopolysaccharides, Male, Mice, Mice, Transgenic, Microglia, Protein Binding, Protein Biosynthesis, Ribosomes, RNA, Messenger, Serine-Arginine Splicing Factors, Signal Transduction, Transcription, Genetic

Uncontrolled microglial activation may lead to the development of inflammation-induced brain damage. Here, we uncover a ribosome-based mechanism/checkpoint involved in control of the innate immune response and microglial activation. Using an in vivo model system for analysis of the dynamic translational state of microglial ribosomes, with mRNAs as input and newly synthesized peptides as an output, we find a marked dissociation of microglia mRNA and protein networks following innate immune challenge. Highly upregulated and ribosome-associated mRNAs were not translated, resulting in two distinct microglial molecular signatures, a highly specialized pro-inflammatory mRNA signature and an immunomodulatory/homeostatic protein signature. We find that this is due to specific translational suppression of highly expressed mRNAs through a 3' UTR-mediated mechanism involving the RNA-binding protein SRSF3. This discovery suggests avenues for therapeutic modulation of innate immune response in resident microglia.

Alternate JournalCell Rep
PubMed ID29241548