eIF4E-binding protein regulation of mRNAs with differential 5'-UTR secondary structure: a polyelectrostatic model for a component of protein-mRNA interactions.
Control of translation in eukaryotes is complex, depending on the binding of various factors to mRNAs. Available data for subsets of mRNAs that are translationally up- and down-regulated in yeast eIF4E-binding protein (4E-BP) deletion mutants are coupled with reported mRNA secondary structure measurements to investigate whether 5'-UTR secondary structure varies between the subsets. Genes with up-regulated translational efficiencies in the caf20Δ mutant have relatively high averaged 5'-UTR secondary structure. There is no apparent wide-scale correlation of RNA-binding protein preferences with the increased 5'-UTR secondary structure, leading us to speculate that the secondary structure itself may play a role in differential partitioning of mRNAs between eIF4E/4E-BP repression and eIF4E/eIF4G translation initiation. Both Caf20p and Eap1p contain stretches of positive charge in regions of predicted disorder. Such regions are also present in eIF4G and have been reported to associate with mRNA binding. The pattern of these segments, around the canonical eIF4E-binding motif, varies between each 4E-BP and eIF4G. Analysis of gene ontology shows that yeast proteins containing predicted disordered segments, with positive charge runs, are enriched for nucleic acid binding. We propose that the 4E-BPs act, in part, as differential, flexible, polyelectrostatic scaffolds for mRNAs.
Faculty of Life Sciences, University of Manchester, Manchester Interdisciplinary Biocentre, 131 Princess Street, Manchester M1 7DN, UK.
Andrew
A
Cawley
Jim
J
Warwicker
D020121:5' Untranslated Regions; D039603:Eukaryotic Initiation Factor-4G / Q000737:chemistry; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006639:Histidine / Q000737:chemistry; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010442:Peptide Chain Initiation, Translational; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020539:Sequence Analysis, Protein; D055672:Static Electricity; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D020121:5' Untranslated Regions; C555411:Caf20 protein, S cerevisiae; C555412:Eap1 protein, S cerevisiae; D039603:Eukaryotic Initiation Factor-4G; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D006639:Histidine