title: The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans.
abstract: The microRNA let-7 is a critical regulator of developmental timing events at the larval-to-adult transition in C. elegans. Recently, microRNAs with sequence similarity to let-7 have been identified. We find that doubly mutant animals lacking the let-7 family microRNA genes mir-48 and mir-84 exhibit retarded molting behavior and retarded adult gene expression in the hypodermis. Triply mutant animals lacking mir-48, mir-84, and mir-241 exhibit repetition of L2-stage events in addition to retarded adult-stage events. mir-48, mir-84, and mir-241 function together to control the L2-to-L3 transition, likely by base pairing to complementary sites in the hbl-1 3' UTR and downregulating hbl-1 activity. Genetic analysis indicates that mir-48, mir-84, and mir-241 specify the timing of the L2-to-L3 transition in parallel to the heterochronic genes lin-28 and lin-46. These results indicate that let-7 family microRNAs function in combination to affect both early and late developmental timing decisions.
authors.affiliation: Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
authors.forename: Allison L
authors.initials: AL
authors.lastname: Abbott
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Alvarez-Saavedra
authors.forename: Eric A
authors.initials: EA
authors.lastname: Miska
authors.forename: Nelson C
authors.initials: NC
authors.lastname: Lau
authors.forename: David P
authors.initials: DP
authors.lastname: Bartel
authors.forename: H Robert
authors.initials: HR
authors.lastname: Horvitz
authors.forename: Victor
authors.initials: V
authors.lastname: Ambros
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D010802:Phylogeny; D013997:Time Factors
chemical_list: D029742:Caenorhabditis elegans Proteins; D035683:MicroRNAs; C474488:let-7 microRNA, C elegans