title: Regulatory mutations of mir-48, a C. elegans let-7 family MicroRNA, cause developmental timing defects.
abstract: The C. elegans heterochronic genes program stage-specific temporal identities in multiple tissues during larval development. These genes include the first two miRNA-encoding genes discovered, lin-4 and let-7. We show that lin-58 alleles, identified as lin-4 suppressors, define another miRNA that controls developmental time. These alleles are unique in that they contain point mutations in a gene regulatory element of mir-48, a let-7 family member. mir-48 is expressed prematurely in lin-58 mutants, whereas expression of mir-241, another let-7 family member residing immediately upstream of mir-48, appears to be unaffected. A mir-48 transgene bearing a lin-58 point mutation causes strong precocious phenotypes in the hypodermis and vulva when expressed from multicopy arrays. mir-48::gfp fusions reveal expression in these tissues, and inclusion of a lin-58 mutation causes precocious and enhanced gfp expression. These results suggest that lin-58 alleles disrupt a repressor binding site that restricts the time of miR-48 action in wild-type animals.
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, 55455, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Jones-Rhoades
authors.forename: Nelson C
authors.initials: NC
authors.lastname: Lau
authors.forename: David P
authors.initials: DP
authors.lastname: Bartel
authors.forename: Ann E
authors.initials: AE
authors.lastname: Rougvie
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D013997:Time Factors
chemical_list: D029742:Caenorhabditis elegans Proteins; D035683:MicroRNAs; C474488:let-7 microRNA, C elegans; D049452:Green Fluorescent Proteins