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Translational remodeling by RNA-binding proteins and noncoding RNAs

期刊

出版社

WILEY
DOI: 10.1002/wrna.1647

关键词

translation; proteomics; hypoxia; endothelial; cancer

资金

  1. Sylvester Comprehensive Cancer Center
  2. Canadian Institutes of Health Research grant [MOP 142307]
  3. Heart and Stroke Foundation grant HSF [G-16-00013166]

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Translation plays a crucial role in generating the proteome that regulates phenotype, and recent discoveries have highlighted the importance of system-wide adaptive translational reprogramming in cellular adaptation. Stress-activated RBP networks and ncRNAs have been identified as key players in increasing translation efficiency of transcripts encoding proteins involved in common cellular processes, showcasing a new paradigm in cellular stress adaptation.
Responsible for generating the proteome that controls phenotype, translation is the ultimate convergence point for myriad upstream signals that influence gene expression. System-wide adaptive translational reprogramming has recently emerged as a pillar of cellular adaptation. As classic regulators of mRNA stability and translation efficiency, foundational studies established the concept of collaboration and competition between RNA-binding proteins (RBPs) and noncoding RNAs (ncRNAs) on individual mRNAs. Fresh conceptual innovations now highlight stress-activated, evolutionarily conserved RBP networks and ncRNAs that increase the translation efficiency of populations of transcripts encoding proteins that participate in a common cellular process. The discovery of post-transcriptional functions for long noncoding RNAs (lncRNAs) was particularly intriguing given their cell-type-specificity and historical definition as nuclear-functioning epigenetic regulators. The convergence of RBPs, lncRNAs, and microRNAs on functionally related mRNAs to enable adaptive protein synthesis is a newer biological paradigm that highlights their role as translatome (protein output) remodelers and reinvigorates the paradigm of RNA operons. Together, these concepts modernize our understanding of cellular stress adaptation and strategies for therapeutic development. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications Translation > Translation Regulation Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

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