Regulatory mutations of mir-48, a C. elegans let-7 family MicroRNA, cause developmental timing defects.
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.
Li
Ming
M
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, 55455, USA.
Jones-Rhoades
Matthew W
MW
Lau
Nelson C
NC
Bartel
David P
DP
Rougvie
Ann E
AE
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
D029742:Caenorhabditis elegans Proteins; D035683:MicroRNAs; C474488:let-7 microRNA, C elegans; D049452:Green Fluorescent Proteins