The SXL-UNR corepressor complex uses a PABP-mediated mechanism to inhibit ribosome recruitment to msl-2 mRNA.
Drosophila female viability requires translational repression of msl-2 mRNA by the SXL-UNR 3' UTR corepressor complex, which inhibits ribosome recruitment by an unknown mechanism. Here, we reveal a key role for the poly(A)-binding protein (PABP), a translational activator, in this inhibitory mechanism. Efficient msl-2 mRNA silencing via the 3' UTR requires both a poly(A) tail and PABP function, and we find that UNR directly interacts with PABP. To investigate how the repressor complex and PABP affect RNP composition during early steps in translation initiation, we established direct biochemical assays for synergistic recruitment of eIF4F and ribosomes by the cap and poly(A) tail. We find that the repressor complex targets ribosome binding after PABP-mediated recruitment of eIF4E/G. Our results uncover an important regulatory mechanism of Drosophila dosage compensation and provide insight into PABP-dependent translational control by 3' UTR-bound regulatory proteins.
Duncan
Kent E
KE
European Molecular Biology Laboratory, Heidelberg, Germany.
Strein
Claudia
C
Hentze
Matthias W
MW
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002846:Chromatography, Affinity; D056970:Co-Repressor Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D011061:Poly A / Q000378:metabolism; D039122:Poly(A)-Binding Protein I / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D054657:Ribosome Subunits / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D020413:3' Untranslated Regions; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D009687:Nuclear Proteins; D039122:Poly(A)-Binding Protein I; D012315:RNA Caps; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C067777:Sxl protein, Drosophila; D014157:Transcription Factors; C509278:UNR protein, Drosophila; C094166:msl-2 protein, Drosophila; D011061:Poly A