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Binding to the ribosome by eIF4B drives yeast translational control in response to membrane stressors
Author(s) -
Walker Sarah E,
Liu Xiaozhuo E,
Moshiri Houtan E
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.628.4
Subject(s) - initiation factor , eif4a , eukaryotic initiation factor , ribosome , chemistry , ribosome profiling , microbiology and biotechnology , translation (biology) , eukaryotic translation , biochemistry , eukaryotic ribosome , messenger rna , protein biosynthesis , rna , biology , gene
The eIF4 group of eukaryotic translation initiation factors promotes mRNA binding to the ribosome. Increased levels or activities of these factors have been associated with a number of human diseases, highlighting the need for additional mechanistic information for these proteins. Our previous work indicated that ribosome binding by the N‐terminal domain of yeast eIF4B is critical for robust initiation in vitro and in vivo. In contrast, RNA‐binding activities by the RRM domain of eIF4B were dispensable. Our work left open the possibility that the RRM of eIF4B could allow for enhanced translation under stress conditions. Here we have compared the effects of disrupting RNA and ribosome binding of yeast eIF4B under ~1400 different growth conditions. The RRM was dispensable for vegetative growth in all conditions tested, but we found that ribosome binding promotes growth in response to a number of stressors through changes in translation. In particular, the NTD confers a strong growth advantage in the presence of the denaturing reagent, Urea and a number of other osmolytes that require robust cellular integrity for survival. Ribosome profiling of cells with and without the ribosome‐binding NTD of eIF4B reveals gross changes in translation of mRNAs containing longer than average and highly structured 5‐prime untranslated regions in response to Urea stress. These changes are dependent on the ribosome‐binding activity of eIF4B, which suggests eIF4B regulates mRNA recruitment as a part of the ribosomal preinitiation complex rather than by activating isolated mRNPs prior to ribosome binding. This analysis indicates the cellular response to urea in yeast includes a translational component, driven by increased translation of proteins associated with the cellular periphery. The results of these studies highlight the importance of the general translation factor eIF4B in adapting to external conditions, and allow us to tie the mechanical functions of this translation factor to specific cellular phenotypes. Support or Funding Information This work is supported by NIH grant R00GM119173 and startup funds from SUNY at Buffalo‐College of Arts and Sciences. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .