RT Journal Article SR Electronic T1 Widespread shortening of 3’ untranslated regions and increased exon inclusion are evolutionarily conserved features of innate immune responses to infection JF bioRxiv FD Cold Spring Harbor Laboratory SP 026831 DO 10.1101/026831 A1 Athma A. Pai A1 Golshid Baharian A1 Ariane Pagé Sabourin A1 Jessica F. Brinkworth A1 Yohann Nédélec A1 Joseph W. Foley A1 Jean-Christophe Grenier A1 Katherine J. Siddle A1 Anne Dumaine A1 Vania Yotova A1 Zachary P. Johnson A1 Robert E. Lanford A1 Christopher B. Burge A1 Luis B. Barreiro YR 2016 UL http://biorxiv.org/content/early/2016/04/20/026831.abstract AB 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.