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Identifying eIF4E-binding protein translationally-controlled transcripts reveals links to mRNAs bound by specific PUF proteins.

Nucleic acids research | Dec 14, 2010

eIF4E-binding proteins (4E-BPs) regulate translation of mRNAs in eukaryotes. However the extent to which specific mRNA targets are regulated by 4E-BPs remains unknown. We performed translational profiling by microarray analysis of polysome and monosome associated mRNAs in wild-type and mutant cells to identify mRNAs in yeast regulated by the 4E-BPs Caf20p and Eap1p; the first-global comparison of 4E-BP target mRNAs. We find that yeast 4E-BPs modulate the translation of >1000 genes. Most target mRNAs differ between the 4E-BPs revealing mRNA specificity for translational control by each 4E-BP. This is supported by observations that eap1Δ and caf20Δ cells have different nitrogen source utilization defects, implying different mRNA targets. To account for the mRNA specificity shown by each 4E-BP, we found correlations between our data sets and previously determined targets of yeast mRNA-binding proteins. We used affinity chromatography experiments to uncover specific RNA-stabilized complexes formed between Caf20p and Puf4p/Puf5p and between Eap1p and Puf1p/Puf2p. Thus the combined action of each 4E-BP with specific 3'-UTR-binding proteins mediates mRNA-specific translational control in yeast, showing that this form of translational control is more widely employed than previously thought.

Pubmed ID: 20705650 RIS Download

Mesh terms: Amino Acids | Cyclins | Eukaryotic Initiation Factors | Gene Deletion | Gene Expression Regulation, Fungal | Nitrogen | Oligonucleotide Array Sequence Analysis | Protein Biosynthesis | RNA, Messenger | RNA-Binding Proteins | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins | Transcription Factors | Transcription, Genetic

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Associated grants

  • Agency: Biotechnology and Biological Sciences Research Council, Id: BB_BB/F019483/1
  • Agency: Biotechnology and Biological Sciences Research Council, Id: BB_BB/E024181/1
  • Agency: Biotechnology and Biological Sciences Research Council, Id: BB_BB/E011888/1
  • Agency: Biotechnology and Biological Sciences Research Council, Id: BB_BB/G012571/1
  • Agency: Biotechnology and Biological Sciences Research Council, Id: BBG012571
  • Agency: Biotechnology and Biological Sciences Research Council, Id: BBD000106
  • Agency: Biotechnology and Biological Sciences Research Council, Id: G17520

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