Translation initiation factor eIF4G1 preferentially binds yeast transcript leaders containing conserved oligo-uridine motifs

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...

Full description

Saved in:
Bibliographic Details
Published in:RNA (Cambridge) 2017-09, Vol.23 (9), p.1365-1375
Main Authors: Zinshteyn, Boris, Rojas-Duran, Maria F, Gilbert, Wendy V
Format: Article
Language:English
Subjects:
Binding Sites
Cellular stress response
Conserved Sequence
Eukaryotic Initiation Factor-4G - metabolism
Gene expression
Gene Expression Regulation, Fungal
Initiation factor eIF-4G
Nucleotide Motifs
Nucleotide sequence
Poly U - metabolism
Protein Binding
Protein Biosynthesis
RNA, Messenger - chemistry
RNA, Messenger - genetics
RNA, Messenger - metabolism
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Transcription
Uridine
Yeast
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1355-8382
1469-9001
DOI:10.1261/rna.062059.117