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Rps26 directs mRNA-specific translation by recognition of Kozak sequence elements

ABSTRACT: The “Kozak sequence”, immediately upstream of the start codon, regulates the translational efficiency of an mRNA. Nevertheless, how this sequence is recognized remains unexplored. Here, we describe a novel approach to separate two ribosome populations from the same cells and use this method, and RNA-seq, to identify the mRNAs bound to ribosomes with and without Rps26, a protein linked to the pathogenesis of Diamond Blackfan Anemia (DBA). These analyses reveal that Rps26 contributes to recognition of the Kozak sequence in well-translated mRNAs, and that Rps26-deficient ribosomes preferentially translate mRNA from select stress response pathways. Surprisingly, we demonstrate that exposure of cells to these stresses leads to the formation of Rps26-deficient ribosomes and to the translation of their targets. Thus, Rps26-deficient ribosomes play aberrant pathogenic roles in DBA as well as physiological roles in augmenting the well-characterized stress transcriptional response with a heretofore unknown translational stress response, thereby creating a feed forward loop in gene-expression.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE86203 | GEO | 2017/07/30

SECONDARY ACCESSION(S): PRJNA340886

REPOSITORIES: GEO

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