Widespread generation of alternative UTRs contributes to sex-specific RNA binding by UNR

RNA. 2012 Jan;18(1):53-64. doi: 10.1261/rna.029603.111. Epub 2011 Nov 18.

Abstract

Upstream of N-ras (UNR) is a conserved RNA-binding protein that regulates mRNA translation and stability by binding to sites generally located in untranslated regions (UTRs). In Drosophila, sex-specific binding of UNR to msl2 mRNA and the noncoding RNA roX is believed to play key roles in the control of X-chromosome dosage compensation in both sexes. To investigate broader sex-specific functions of UNR, we have identified its RNA targets in adult male and female flies by high-throughput RNA binding and transcriptome analysis. Here we show that UNR binds to a large set of protein-coding transcripts and to a smaller set of noncoding RNAs in a sex-specific fashion. The analyses also reveal a strong correlation between sex-specific binding of UNR and sex-specific differential expression of UTRs in target genes. Validation experiments indicate that UNR indeed recognizes sex-specifically processed transcripts. These results suggest that UNR exploits the transcript diversity generated by alternative processing and alternative promoter usage to bind and regulate target genes in a sex-specific manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Female
  • Male
  • Nuclear Proteins / genetics*
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Sex Factors
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • Untranslated Regions*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • UNR protein, Drosophila
  • Untranslated Regions
  • msl-2 protein, Drosophila