Surveying the global landscape of post-transcriptional regulators.

Surveying the global landscape of post-transcriptional regulators.
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DOI:
10.1038/s41594-023-00999-5
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发表时间:
2023-06
影响因子:
16.8
通讯作者:
Ingolia NT
Ingolia NT
中科院分区:
生物学1区
文献类型:
--
作者:
Reynaud K;McGeachy AM;Noble D;Meacham ZA;Ingolia NT

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Numerous proteins regulate gene expression by modulating mRNA translation and decay. To uncover the full scope of these post-transcriptional regulators, we conducted an unbiased survey that quantifies regulatory activity across the budding yeast proteome and delineates the protein domains responsible for these effects. Our approach couples a tethered function assay with quantitative single-cell fluorescence measurements to analyze ~50,000 protein fragments and determine their effects on a tethered mRNA. We characterize hundreds of strong regulators, which are enriched for canonical and unconventional mRNA-binding proteins. Regulatory activity typically maps outside the RNA-binding domains themselves, highlighting a modular architecture that separates mRNA targeting from post-transcriptional regulation. Activity often aligns with intrinsically disordered regions that can interact with other proteins, even in core mRNA translation and degradation factors. Our results thus reveal networks of interacting proteins that control mRNA fate and illuminate the molecular basis for post-transcriptional gene regulation. A systematic survey of the budding yeast proteome identifies hundreds of post-transcriptional regulators. Regulatory activity is enriched in RNA-binding proteins but lies outside the RNA-binding domains, often within intrinsically disordered regions.
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