Sex-lethal imparts a sex-specific function to UNR by recruiting it to the msl-2 mRNA 3' UTR: translational repression for dosage compensation

Genes Dev. 2006 Feb 1;20(3):368-79. doi: 10.1101/gad.371406.

Abstract

MSL-2 (male-specific lethal 2) is the limiting component of the Drosophila dosage compensation complex (DCC) that specifically increases transcription from the male X chromosome. Ectopic expression of MSL-2 protein in females causes DCC assembly on both X chromosomes and lethality. Inhibition of MSL-2 synthesis requires the female-specific protein sex-lethal (SXL), which binds to the msl-2 mRNA 5' and 3' untranslated regions (UTRs) and blocks translation through distinct UTR-specific mechanisms. Here, we purify translationally silenced msl-2 mRNPs and identify UNR (upstream of N-ras) as a protein recruited to the 3' UTR by SXL. We demonstrate that SXL requires UNR as a corepressor for 3'-UTR-mediated regulation, imparting a female-specific function to the ubiquitously expressed UNR protein. Our results reveal a novel functional role for UNR as a translational repressor and indicate that UNR is a key component of a "fail-safe" dosage compensation regulatory system that prevents toxic MSL-2 synthesis in female cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3' Untranslated Regions / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cytoplasm / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology*
  • Dosage Compensation, Genetic*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology*
  • Female
  • Humans
  • Male
  • Models, Biological
  • Models, Genetic
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Biosynthesis / genetics
  • Protein Biosynthesis / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism
  • Sequence Homology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection

Substances

  • 3' Untranslated Regions
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • Sxl protein, Drosophila
  • Transcription Factors
  • UNR protein, Drosophila
  • messenger ribonucleoprotein
  • msl-2 protein, Drosophila