title: Global mRNA selection mechanisms for translation initiation.
abstract: BACKGROUND
  The selection and regulation of individual mRNAs for translation initiation from a competing pool of mRNA are poorly understood processes. The closed loop complex, comprising eIF4E, eIF4G and PABP, and its regulation by 4E-BPs are perceived to be key players. Using RIP-seq, we aimed to evaluate the role in gene regulation of the closed loop complex and 4E-BP regulation across the entire yeast transcriptome.
  
  
  RESULTS
  We find that there are distinct populations of mRNAs with coherent properties: one mRNA pool contains many ribosomal protein mRNAs and is enriched specifically with all of the closed loop translation initiation components. This class likely represents mRNAs that rely heavily on the closed loop complex for protein synthesis. Other heavily translated mRNAs are apparently under-represented with most closed loop components except Pab1p. Combined with data showing a close correlation between Pab1p interaction and levels of translation, these data suggest that Pab1p is important for the translation of these mRNAs in a closed loop independent manner. We also identify a translational regulatory mechanism for the 4E-BPs; these appear to self-regulate by inhibiting translation initiation of their own mRNAs.
  
  
  CONCLUSIONS
  Overall, we show that mRNA selection for translation initiation is not as uniformly regimented as previously anticipated. Components of the closed loop complex are highly relevant for many mRNAs, but some heavily translated mRNAs interact poorly with this machinery. Therefore, alternative, possibly Pab1p-dependent mechanisms likely exist to load ribosomes effectively onto mRNAs. Finally, these studies identify and characterize a complex self-regulatory circuit for the yeast 4E-BPs.
authors: Joseph
authors: J
authors: Costello
authors: Lydia M
authors: LM
authors: Castelli
authors: William
authors: W
authors: Rowe
authors: Christopher J
authors: CJ
authors: Kershaw
authors: David
authors: D
authors: Talavera
authors: Sarah S
authors: SS
authors: Mohammad-Qureshi
authors: Paul F G
authors: PF
authors: Sims
authors: Christopher M
authors: CM
authors: Grant
authors: Graham D
authors: GD
authors: Pavitt
authors: Simon J
authors: SJ
authors: Hubbard
authors: Mark P
authors: MP
authors: Ashe
mesh_terms: D016000:Cluster Analysis; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D047468:Immunoprecipitation / Q000379:methods; D008954:Models, Biological; D010442:Peptide Chain Initiation, Translational; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
chemical_list: D039642:Eukaryotic Initiation Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins
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