期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 24, 期 9, 页码 700-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.3442
关键词
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资金
- US National Institutes of Health [R01-GM086451, F31-GM116406]
- PGA National (Women's Cancer Awareness Day fellowship)
- Richard AMP
- Helen DeVos Foundation
- Howard Hughes Medical Institute [55108536]
We describe a novel approach to separate two ribosome populations from the same cells and use this method in combination with RNA-seq to identify mRNAs bound to Saccharomyces cerevisiae ribosomes with and without Rps26, a protein linked to the pathogenesis of Diamond-Blackfan anemia (DBA). These analyses reveal that Rps26 contributes to mRNA-specific translation by recognition of the Kozak sequence in well-translated mRNAs and that Rps26-deficient ribosomes preferentially translate mRNA from select stress-response pathways. Surprisingly, exposure of yeast to these stresses leads to the formation of Rps26-deficient ribosomes and to the increased translation of their target mRNAs. These results describe a novel paradigm: the production of specialized ribosomes, which play physiological roles in augmenting the well-characterized transcriptional stress response with a heretofore unknown translational response, thereby creating a feed-forward loop in gene expression. Moreover, the simultaneous gain-of-function and loss-of-function phenotypes from Rps26-deficient ribosomes can explain the pathogenesis of DBA.
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