title: A negative regulatory loop between microRNA and Hox gene controls posterior identities in Caenorhabditis elegans.
abstract: MicroRNAs (miRNAs) have been found to regulate gene expression across eukaryotic species, but the function of most miRNA genes remains unknown. Here we describe how the analysis of the expression patterns of a well-conserved miRNA gene, mir-57, at cellular resolution for every minute during early development of Caenorhabditis elegans provided key insights in understanding its function. Remarkably, mir-57 expression shows strong positional bias but little tissue specificity, a pattern reminiscent of Hox gene function. Despite the minor defects produced by a loss of function mutation, overexpression of mir-57 causes dramatic posterior defects, which also mimic the phenotypes of mutant alleles of a posterior Hox gene, nob-1, an Abd homolog. More importantly, nob-1 expression is found in the same two posterior AB sublineages as those expressing mir-57 but with an earlier onset. Intriguingly, nob-1 functions as an activator for mir-57 expression; it is also a direct target of mir-57. In agreement with this, loss of mir-57 function partially rescues the nob-1 allele defects, indicating a negative feedback regulatory loop between the miRNA and Hox gene to provide positional cues. Given the conservation of the miRNA and Hox gene, the regulatory mechanism might be broadly used across species. The strategy used here to explore mir-57 function provides a path to dissect the regulatory relationship between genes.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America. zyzhao@u.washington.edu
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Zhao
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Boyle
authors.forename: Zongzhi
authors.initials: Z
authors.lastname: Liu
authors.forename: John I
authors.initials: JI
authors.lastname: Murray
authors.forename: William B
authors.initials: WB
authors.lastname: Wood
authors.forename: Robert H
authors.initials: RH
authors.lastname: Waterston
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D019070:Cell Lineage; D015536:Down-Regulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; C408064:NOB-1 protein, C elegans; D014157:Transcription Factors
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