Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Division of Hematology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Wiley Interdiscip Rev RNA. 2021 Sep;12(5):e1647. doi: 10.1002/wrna.1647. Epub 2021 Mar 10.
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.
负责生成控制表型的蛋白质组,翻译是影响基因表达的无数上游信号的最终汇聚点。系统范围的适应性翻译重编程最近成为细胞适应的支柱之一。作为 mRNA 稳定性和翻译效率的经典调节剂,基础研究确立了 RNA 结合蛋白 (RBP) 和非编码 RNA (ncRNA) 在单个 mRNA 上协作和竞争的概念。现在,新的概念创新强调了应激激活的、进化保守的 RBP 网络和 ncRNA,它们提高了参与共同细胞过程的蛋白质编码转录物群体的翻译效率。长非编码 RNA (lncRNA) 的转录后功能的发现尤其引人注目,因为它们具有细胞特异性,并被历史上定义为核功能的表观遗传调节剂。RBP、lncRNA 和 microRNA 在功能相关的 mRNA 上的汇聚,以实现适应性蛋白质合成,这是一个新的生物学范例,突出了它们作为“转录组(蛋白质输出)重塑因子”的作用,并重新激发了“RNA 操纵子”的范例。这些概念共同使我们对细胞应激适应和治疗开发策略的理解现代化。本文归类于:RNA 与蛋白质和其他分子的相互作用 > 蛋白质-RNA 相互作用:功能意义 翻译 > 翻译调控 调控 RNA/RNAi/核糖开关 > 调控 RNA。