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Surveying the global landscape of post-transcriptional regulators.

ABSTRACT: 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.

SUBMITTER: Reynaud K

PROVIDER: S-EPMC10279529 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Surveying the global landscape of post-transcriptional regulators.

Reynaud Kendra K McGeachy Anna M AM Noble David D Meacham Zuriah A ZA Ingolia Nicholas T NT

Nature structural & molecular biology 20230525 6

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 tether ...[more]

PMID: 37231154

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Project description:BACKGROUND: There is growing interest in global health among medical trainees. Medical schools and residencies are responding to this trend by offering global health opportunities within their programs. Among United States (US) graduating pediatric residents, 40% choose to subspecialize after residency training. There is limited data, however, regarding global health opportunities within traditional post-residency, subspecialty fellowship training programs. The objectives of this study were to explore the availability and type of global health opportunities within Accreditation Council for Graduate Medical Education (ACGME)-accredited pediatric subspecialty fellowship training programs, as noted by their online report, and to document change in these opportunities over time. METHODS: The authors performed a systematic online review of ACGME-accredited fellowship training programs within a convenience sample of six US pediatric subspecialties. Utilizing two data sources, the American Medical Association-Fellowship and Residency Electronic Interactive Database Access (AMA-FREIDA) and individual program websites, all programs were coded for global health opportunities and opportunity types were stratified into predefined categories. Comparisons were made between 2008 and 2011 using Fisher exact test. All analyses were conducted using SAS Software v. 9.3 (SAS Institute Inc., Cary, NC). RESULTS: Of the 355 and 360 programs reviewed in 2008 and 2011 respectively, there was an increase in total number of programs listing global health opportunities on AMA-FREIDA (16% to 23%, p=0.02) and on individual program websites (8% to 16%, p=0.004). Nearly all subspecialties had an increased percentage of programs offering global health opportunities on both data sources; although only critical care experienced a significant increase (p=0.04, AMA-FREIDA). The types of opportunities differed across all subspecialties. CONCLUSIONS: Global health opportunities among ACGME-accredited pediatric subspecialty fellowship programs are limited, but increasing as noted by their online report. The availability and types of these opportunities differ by pediatric subspecialty.

Dataset Information

Surveying the global landscape of post-transcriptional regulators.

Publications

Surveying the global landscape of post-transcriptional regulators.

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