Regulatory mutations of mir-48, a C. elegans let-7 family MicroRNA, cause developmental timing defects

Dev Cell. 2005 Sep;9(3):415-22. doi: 10.1016/j.devcel.2005.08.002.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / ultrastructure
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism*
  • Gene Expression Regulation, Developmental*
  • Genotype
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Mutation
  • Time Factors

Substances

  • Caenorhabditis elegans Proteins
  • MicroRNAs
  • let-7 microRNA, C elegans
  • Green Fluorescent Proteins