Widespread shortening of 3’ untranslated regions and increased exon inclusion are evolutionarily conserved features of innate immune responses to infection

The contribution of pre-mRNA processing mechanisms to the regulation of immune responses remains poorly studied despite emerging examples of their role as regulators of immune defenses. Here, we used mRNA sequencing to quantify gene expression and isoform abundances in primary macrophages from 60 individuals, before and after infection with two live bacteria. In response to both bacteria we identified thousands of genes that significantly change isoform usage in response to infection, and found global shifts towards (i) the inclusion of cassette exons and (ii) shorter 3 UTRs. Using complementary data collected in non-human primates, we show that these features are evolutionarily conserved among primates. Finally, our results suggest that the pervasive usage of shorter 3 UTRs is a mechanism for particular genes to evade repression by immune-activated miRNAs. Collectively, our results show that dynamic changes in RNA processing play a key role in the regulation of innate immune responses.