Xenopus furry contributes to release of microRNA gene silencing

Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19344-9. doi: 10.1073/pnas.1008954107. Epub 2010 Oct 25.

Abstract

A transcriptional corepressor, Xenopus furry (Xfurry), is expressed in the chordamesodermal region and induces secondary dorsal axes when overexpressed on the ventral side of the embryo. The N-terminal furry domain functions as a repressor, and the C-terminal leucine zipper (LZ) motifs /coiled-coil structure, found only in vertebrate homologs, contributes to the nuclear localization. The engrailed repressor (enR)+LZ repressor construct, which has properties similar to Xfurry, induced several chordamesodermal genes. In contrast, an antisense morpholino oligonucleotide, Xfurry-MO, and the activating construct, herpes simplex virus protein (VP16)+LZ, had effects opposite those of Xfurry overexpression. Because blocking protein synthesis with cycloheximide superinduced several Xfurry transcriptional targets, and because expression of enR+LZ induced such genes under cycloheximide treatment, we analyzed the role of an Xfurry transcriptional target, microRNA miR-15. Cycloheximide reduced the expression of primary miR-15 (pri-miR-15), whereas miR-15 reduced the expression of genes superinduced by cycloheximide treatment. These results show that Xfurry regulates chordamesodermal genes by contributing to repression of pretranscriptional gene silencing by miR-15.

Publication types

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

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cycloheximide / pharmacology
  • Gene Expression Regulation
  • Gene Silencing*
  • MicroRNAs / genetics*
  • Notochord
  • Repressor Proteins / genetics*
  • Xenopus Proteins / genetics*
  • Xenopus Proteins / physiology
  • Xenopus laevis / genetics*

Substances

  • FRY protein, Xenopus
  • MicroRNAs
  • Repressor Proteins
  • Xenopus Proteins
  • Cycloheximide