Differential Expression Data from Mice 24hrs after stroke

Microglial activation after stroke may lead to development of inflammation-induced brain damage. Here we uncover a ribosome-based mechanism/check point involved in control of the innate immune response and microglial activation orchestrated by RNA binding protein SRSF3. 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 found a marked dissociation of microglia mRNA and protein signatures following ischemic stroke. Highly up-regulated and ribosomes associated mRNAs were not translated 24hrs after stroke resulting in two distinct microglial molecular signatures, a highly specialized pro-inflammatory mRNA and immunomodulatory/homeostatic protein signatures. We found 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 after stroke. Transgenic mice expressing Flag/EGFP-RPL10a under the control of CD11b promoter were used to perform transcriptomic analysis in stroked and CTL mice. RNA was extracted according to the TRAP protocol and hybridized on Affymetrix microarrays (MoGene-2_0-st). The mice were used at 2-3 months old with equal ratio of male/female. Array data was processed by Transcriptome Analysis Console 3.0 (TAC). No technical replicates were performed.