title: bacterial infection drives the expression dynamics of microRNAs and their isomiRs.
abstract: The optimal coordination of the transcriptional response of host cells to infection is essential for establishing appropriate immunological outcomes. In this context, the role of microRNAs (miRNAs)--important epigenetic regulators of gene expression--in regulating mammalian immune systems is increasingly well recognised. However, the expression dynamics of miRNAs, and that of their isoforms, in response to infection remains largely unexplored. Here, we characterized the genome-wide miRNA transcriptional responses of human dendritic cells, over time, to various mycobacteria differing in their virulence as well as to other bacteria outside the genus Mycobacterium, using small RNA-sequencing. We detected the presence of a core temporal response to infection, shared across bacteria, comprising 49 miRNAs, highlighting a set of miRNAs that may play an essential role in the regulation of basic cellular responses to stress. Despite such broadly shared expression dynamics, we identified specific elements of variation in the miRNA response to infection across bacteria, including a virulence-dependent induction of the miR-132/212 family in response to mycobacterial infections. We also found that infection has a strong impact on both the relative abundance of the miRNA hairpin arms and the expression dynamics of miRNA isoforms. That we observed broadly consistent changes in relative arm expression and isomiR distribution across bacteria suggests that this additional, internal layer of variability in miRNA responses represents an additional source of subtle miRNA-mediated regulation upon infection. Collectively, this study increases our understanding of the dynamism and role of miRNAs in response to bacterial infection, revealing novel features of their internal variability and identifying candidate miRNAs that may contribute to differences in the pathogenicity of mycobacterial infections.
authors: Institut Pasteur, Unit of Human Evolutionary Genetics, Paris, France; Centre National de la Recherche Scientifique, Paris, France.
authors: Katherine J
authors: KJ
authors: Siddle
authors: Institut Pasteur, Unit of Mycobacterial Genetics, Paris, France.
authors: Ludovic
authors: L
authors: Tailleux
authors: Institut Pasteur, Unit of Human Evolutionary Genetics, Paris, France; Centre National de la Recherche Scientifique, Paris, France; Université Pierre et Marie Curie, Cellule Pasteur UPMC, Paris, France.
authors: Matthieu
authors: M
authors: Deschamps
authors: Institut Pasteur, Unit of Human Evolutionary Genetics, Paris, France; Centre National de la Recherche Scientifique, Paris, France.
authors: Yong-Hwee Eddie
authors: YH
authors: Loh
authors: Fasteris SA, Plan-les-Ouates, Switzerland.
authors: Cécile
authors: C
authors: Deluen
authors: Institut Pasteur, Unit of Mycobacterial Genetics, Paris, France.
authors: Brigitte
authors: B
authors: Gicquel
authors: Université Pierre et Marie Curie, Laboratory of Developmental Biology, Paris, France.
authors: Christophe
authors: C
authors: Antoniewski
authors: Ste-Justine Hospital Research Centre and Department of Paediatrics, Faculty of Medicine, University of Montréal, Montréal, Canada.
authors: Luis B
authors: LB
authors: Barreiro
authors: Fasteris SA, Plan-les-Ouates, Switzerland.
authors: Laurent
authors: L
authors: Farinelli
authors: Institut Pasteur, Unit of Human Evolutionary Genetics, Paris, France; Centre National de la Recherche Scientifique, Paris, France.
authors: Lluís
authors: L
authors: Quintana-Murci
mesh_terms: D001424:Bacterial Infections / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity; D016415:Sequence Alignment
chemical_list: D035683:MicroRNAs