title: Functional overlap between eIF4G isoforms in Saccharomyces cerevisiae.
abstract: Initiation factor eIF4G is a key regulator of eukaryotic protein synthesis, recognizing proteins bound at both ends of an mRNA to help recruit messages to the small (40S) ribosomal subunit. Notably, the genomes of a wide variety of eukaryotes encode multiple distinct variants of eIF4G. We found that deletion of eIF4G1, but not eIF4G2, impairs growth and global translation initiation rates in budding yeast under standard laboratory conditions. Not all mRNAs are equally sensitive to loss of eIF4G1; genes that encode messages with longer poly(A) tails are preferentially affected. However, eIF4G1-deletion strains contain significantly lower levels of total eIF4G, relative to eIF4G2-delete or wild type strains. Homogenic strains, which encode two copies of either eIF4G1 or eIF4G2 under native promoter control, express a single isoform at levels similar to the total amount of eIF4G in a wild type cell and have a similar capacity to support normal translation initiation rates. Polysome microarray analysis of these strains and the wild type parent showed that translationally active mRNAs are similar. These results suggest that total eIF4G levels, but not isoform-specific functions, determine mRNA-specific translational efficiency.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.
authors.forename: Bryan K
authors.initials: BK
authors.lastname: Clarkson
authors.forename: Wendy V
authors.initials: WV
authors.lastname: Gilbert
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Doudna
mesh_terms: D001483:Base Sequence; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D039562:Eukaryotic Initiation Factor-4F / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017384:Sequence Deletion
chemical_list: D039562:Eukaryotic Initiation Factor-4F; D039603:Eukaryotic Initiation Factor-4G; D020033:Protein Isoforms; D029701:Saccharomyces cerevisiae Proteins; C107740:TIF4631 protein, S cerevisiae; C107741:TIF4632 protein, S cerevisiae