RRC ID 45633
著者 Ren Z, Ambros VR.
タイトル Caenorhabditis elegans microRNAs of the let-7 family act in innate immune response circuits and confer robust developmental timing against pathogen stress.
ジャーナル Proc Natl Acad Sci U S A
Abstract Animals maintain their developmental robustness against natural stresses through numerous regulatory mechanisms, including the posttranscriptional regulation of gene expression by microRNAs (miRNAs). Caenorhabditis elegans miRNAs of the let-7 family (let-7-Fam) function semiredundantly to confer robust stage specificity of cell fates in the hypodermal seam cell lineages. Here, we show reciprocal regulatory interactions between let-7-Fam miRNAs and the innate immune response pathway in C. elegans. Upon infection of C. elegans larvae with the opportunistic human pathogen Pseudomonas aeruginosa, the developmental timing defects of certain let-7-Fam miRNA mutants are enhanced. This enhancement is mediated by the p38 MAPK innate immune pathway acting in opposition to let-7-Fam miRNA activity, possibly via the downstream Activating Transcription Factor-7 (ATF-7). Furthermore, let-7-Fam miRNAs appear to exert negative regulation on the worm's resistance to P. aeruginosa infection. Our results show that the inhibition of pathogen resistance by let-7 involves downstream heterochronic genes and the p38 MAPK pathway. These findings suggest that let-7-Fam miRNAs are integrated into innate immunity gene regulatory networks, such that this family of miRNAs modulates immune responses while also ensuring robust timing of developmental events under pathogen stress.
巻・号 112(18)
ページ E2366-75
公開日 2015-5-5
DOI 10.1073/pnas.1422858112
PII 1422858112
PMID 25897023
PMC PMC4426397
MeSH Alleles Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / immunology Cell Lineage Gene Expression Regulation Gene Regulatory Networks Genes, Reporter Immune System Immunity, Innate* MicroRNAs / metabolism* Microscopy, Confocal Microscopy, Electron, Transmission Mutation Phenotype Pseudomonas Infections / metabolism Pseudomonas aeruginosa Signal Transduction Treatment Outcome p38 Mitogen-Activated Protein Kinases / metabolism
IF 9.412
引用数 47
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm3036