Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
Fardin Ghobakhlou
Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
David J Young
Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States; Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United States
Jyothsna Visweswaraiah
Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
In eukaryotes, 43S preinitiation complex (PIC) formation is a rate-determining step of translation. Ribosome recycling following translation termination produces free 40S subunits for re-assembly of 43S PICs. Yeast mutants lacking orthologs of mammalian eIF2D (Tma64), and either MCT-1 (Tma20) or DENR (Tma22), are broadly impaired for 40S recycling; however, it was unknown whether this defect alters the translational efficiencies (TEs) of particular mRNAs. Here, we conducted ribosome profiling of a yeast tma64∆/tma20∆ double mutant and observed a marked reprogramming of translation, wherein the TEs of the most efficiently translated (‘strong’) mRNAs increase, while those of ‘weak’ mRNAs generally decline. Remarkably, similar reprogramming was seen on reducing 43S PIC assembly by inducing phosphorylation of eIF2α or by decreasing total 40S subunit levels by depleting Rps26. Our findings suggest that strong mRNAs outcompete weak mRNAs in response to 43S PIC limitation achieved in various ways, in accordance with previous mathematical modeling.