GSBS Student Publications

Student Author(s)

Zhiji Ren

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Program in Molecular Medicine; RNA Therapeutics Institute

Date

5-5-2015

Document Type

Article

Medical Subject Headings

Alleles; Animals; Caenorhabditis elegans; Cell Lineage; Gene Expression Regulation; Gene Regulatory Networks; Genes, Reporter; Immune System; *Immunity, Innate; MicroRNAs; Microscopy, Confocal; Microscopy, Electron, Transmission; Mutation; Phenotype; Pseudomonas Infections; Pseudomonas aeruginosa; Signal Transduction; Treatment Outcome; p38 Mitogen-Activated Protein Kinases

Disciplines

Developmental Biology | Genetics and Genomics | Immunity | Immunopathology | Molecular Genetics

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.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 2015 May 5;112(18):E2366-75. doi: 10.1073/pnas.1422858112. Epub 2015 Apr 20. Link to article on publisher's site

Comments

Freely available online through the PNAS open access option.

Related Resources

Link to Article in PubMed

Keywords

Pseudomonas aeruginosa, developmental timing, innate immunity, let-7 family microRNAs, p38

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

25897023

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