The Time of Appearance of the C. Elegans let-7 microRNA Is Transcriptionally Controlled Utilizing a Temporal Regulatory Element in Its Promoter

Dev Biol. 2003 Jul 15;259(2):364-79. doi: 10.1016/s0012-1606(03)00202-1.

Abstract

MicroRNAs (miRNAs) are a large family of small regulatory RNAs that are poorly understood. The let-7 miRNA regulates the timing of the developmental switch from larval to adult cell fates during Caenorhabditis elegans development. Expression of let-7 RNA is temporally regulated, with robust expression in the fourth larval and adult stages. Here, we show that, like let-7 RNA, a transcriptional fusion of the let-7 promoter to gfp is temporally regulated, indicating that let-7 is transcriptionally controlled. Temporal upregulation of let-7 transcription requires an enhancer element, the temporal regulatory element (TRE), situated about 1200 base pairs upstream of the start of the mature let-7 RNA. The TRE is both necessary and sufficient for this temporal upregulation. A TRE binding factor (TREB) is able to bind to the TRE, and a 22-base pair inverted repeat within the TRE is necessary and sufficient for this binding. We also find that the nuclear hormone receptor DAF-12 and the RNA binding protein LIN-28 are both required for the correct timing of let-7 RNA and let-7::gfp expression. We speculate that these heterochronic genes regulate let-7 expression through its TRE.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Developmental
  • Genes, Helminth
  • Genes, Switch
  • MicroRNAs / genetics*
  • MicroRNAs / physiology*
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Receptors, Cell Surface
  • Repressor Proteins / metabolism
  • Transcription, Genetic

Substances

  • Caenorhabditis elegans Proteins
  • DAF-1 protein, C elegans
  • LIN-28 protein, C elegans
  • MicroRNAs
  • Receptors, Cell Surface
  • Repressor Proteins
  • let-7 microRNA, C elegans