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Widespread shortening of 3' untranslated regions and increased exon inclusion characterize the human macrophage response to infection

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE73765 | GEO | 2016/09/06

SECONDARY ACCESSION(S): PRJNA297863

REPOSITORIES: GEO

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Widespread shortening of 3' untranslated regions and increased exon inclusion characterize the human macrophage response to infection

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-09-06 | E-GEOD-73765 | biostudies-arrayexpress

Widespread shortening of 3â untranslated regions and increased exon inclusion characterize the human macrophage response to infection [mRNA]

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Widespread shortening of 3â?? untranslated regions and increased exon inclusion characterize the human macrophage response to infection [miRNA]

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Widespread shortening of 3’ untranslated regions and increased exon inclusion characterize the human macrophage response to infection [mRNA]

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Widespread Shortening of 3' Untranslated Regions and Increased Exon Inclusion Are Evolutionarily Conserved Features of Innate Immune Responses to Infection.

Project description: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. We sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infections. Here, we used mRNA sequencing to quantify gene expression and isoform abundances in primary macrophages from 60 individuals, before and after infection with Listeria monocytogenes and Salmonella typhimurium. In response to both bacteria we identified thousands of genes that significantly change isoform usage in response to infection, characterized by an overall increase in isoform diversity after infection. In response to both bacteria, we found global shifts towards (i) the inclusion of cassette exons and (ii) shorter 3' UTRs, with near-universal shifts towards usage of more upstream polyadenylation sites. Using complementary data collected in non-human primates, we show that these features are evolutionarily conserved among primates. Following infection, we identify candidate RNA processing factors whose expression is associated with individual-specific variation in isoform abundance. Finally, by profiling microRNA levels, we show that 3' UTRs with reduced abundance after infection are significantly enriched for target sites for particular miRNAs. These 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 suggest that dynamic changes in RNA processing may play key roles in the regulation of innate immune responses.

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Widespread shortening of 3' untranslated regions and increased exon inclusion characterize the human macrophage response to infection

Project description:Widespread shortening of 3' untranslated regions and increased exon inclusion characterize the human macrophage response to infection

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Evidence for widespread translation of 5' untranslated regions.

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Widespread Effects of Chemokine 3' Untranslated Regions on mRNA Degradation and Protein Production in Human Cells.

Project description:Chemokines are a large family of chemotactic cytokines that play critical roles in inflammation, development, and diseases. Chemokine expression is highly regulated during development and in response to environmental stimuli. The 3' untranslated regions (3'-UTRs) of mRNA are believed to be important in the control of chemokine gene expression. However, the regulatory effects of most chemokine 3'-UTRs have not been characterized previously. In this work, we systematically studied the effects of 43 CC and CXC chemokine 3'-UTRs on gene expression in eight human cell lines and two types of human primary cells. We found that chemokine 3'-UTRs had a wide spectrum of regulatory effects on mRNA abundance and protein production that were tightly correlated with the effects on mRNA stability. In general, 3'-UTRs had remarkably similar effects across all cell types studied. The presence of AU-rich elements, microRNA targets, and Pumilio binding sites were associated with chemokine 3'-UTR activity but did not fully account for all 3'-UTR activity detected using the reporter assay. Mutational analysis illustrated how specific cis-regulatory elements contributed to the regulatory effect of chemokine 3'-UTRs. These findings bring new insights into the mechanisms by which chemokine expression is regulated by 3'-UTRs.

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