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

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

PROVIDER: PRJNA297863 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2529530.fastq.gz	Fastqsanger.gz
	SRR2529540.fastq.gz	Fastqsanger.gz
	SRR2529550.fastq.gz	Fastqsanger.gz
	SRR2529560.fastq.gz	Fastqsanger.gz
	SRR2529570.fastq.gz	Fastqsanger.gz

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

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

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Widespread shortening of 3’ 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 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.

| S-EPMC5045211 | biostudies-literature

Homo sapiens

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

| PRJNA297139 | ENA

Homo sapiens

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

| PRJNA297859 | ENA

Differentiation of syncytialized trophoblasts elicits widespread 3’UTR shortening that accompanies increased cellular function in protein secretion

Project description:Most eukaryotic genes express alternative polyadenylation (APA) isoforms with different 3’UTR sizes. The APA profile varies across tissue types and under different growth and differentiation conditions. Here we report that, unlike many other cell differentiation lineages, differentiation of syncytiotrophoblasts (SCTs) elicits widespread 3’UTR shortening, as shown in multiple in vitro trophoblast differentiation models as well as in single placental cells at different stages of pregnancy. We show that the 3’UTR shortening is unrelated to cell proliferation, a feature previously associated with 3’UTR size control, but rather accompanies increased cell function in protein secretion. In addition, 3’UTR shortening correlates with increased transcript abundance and is coupled with enhanced intronic APA site usage, suggesting activation of 3’ end processing in SCT differentiation. Together, our data indicate that SCTs utilize APA to express transcripts with short 3’UTRs, which may enhance hormone production and secretion, contributing to their functions in pregnancy.

2020-05-15 | GSE138759 | GEO

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