Translation initiation factor eIF4G1 preferentially binds yeast transcript leaders containing conserved oligo-uridine motifs
Name
RNA-2017-Zinshteyn-1365-75.pdf
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4.61 MB
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67898b5ee4a7ba306c0eb79e26291443
Author(s)
Zinshteyn, Boris
Rojas Duran, Maria Fernanda
Gilbert, Wendy
Date Issued
May 2017
Journal
RNA
Publisher
Cold Spring Harbor Laboratory
Citation
Zinshteyn, Boris et al. “Translation Initiation Factor eIF4G1 Preferentially Binds Yeast Transcript Leaders Containing Conserved Oligo-Uridine Motifs.” RNA 23, 9 (May 2017): 1365–1375 © 2017 Zinshteyn et al
Version
Final published version
Abstract
Translational control of gene expression plays essential roles in cellular stress responses and organismal development by enabling rapid, selective, and localized control of protein production. Translational regulation depends on context-dependent differences in the protein output of mRNAs, but the key mRNA features that distinguish efficiently translated mRNAs are largely unknown. Here, we comprehensively determined the RNA-binding preferences of the eukaryotic initiation factor 4G (eIF4G) to assess whether this core translation initiation factor has intrinsic sequence preferences that may contribute to preferential translation of specific mRNAs. We identified a simple RNA sequence motif-oligo-uridine-that mediates high-affinity binding to eIF4G in vitro. Oligo(U) motifs occur naturally in the transcript leader (TL) of hundreds of yeast genes, and mRNAs with unstructured oligo(U) motifs were enriched in immunoprecipitations against eIF4G. Ribosome profiling following depletion of eIF4G in vivo showed preferentially reduced translation of mRNAs with long TLs, including those that contain oligo(U). Finally, TL oligo(U) elements are enriched in genes with regulatory roles and are conserved between yeast species, consistent with an important cellular function. Taken together, our results demonstrate RNA sequence preferences for a general initiation factor, which cells potentially exploit for translational control of specific mRNAs. Keywords: RNA binding; eIF4G; ribosome footprint profiling; transcript leaders; translation initiation
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial 4.0 International
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DOI of Published Version
https://doi.org/10.1261/RNA.062059.117
