Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Mol Cell. 2012 Jan 27;45(2):147-57. doi: 10.1016/j.molcel.2011.12.012.
Cellular pathways are established and maintained by stochastic interactions of highly mobile molecules. The nucleolus plays a central role in the regulation of these molecular networks by capturing and immobilizing proteins. Here, we report a function for noncoding RNA (ncRNA) in the regulation of protein dynamics of key cellular factors, including VHL, Hsp70 and MDM2/PML. Stimuli-specific loci of the nucleolar intergenic spacer produce ncRNA capable of capturing and immobilizing proteins that encode a discrete peptidic code referred to as the nucleolar detention sequence (NoDS). Disruption of the NoDS/intergenic RNA interaction enables proteins to evade nucleolar sequestration and retain their dynamic profiles. Mislocalization of intergenic ncRNA triggers protein immobilization outside of the nucleolus, demonstrating that these ncRNA species can operate independently from the nucleolar architecture. We propose a model whereby protein immobilization by ncRNA is a posttranslational regulatory mechanism.
细胞通路是由高度移动的分子的随机相互作用建立和维持的。核仁通过捕获和固定蛋白质在这些分子网络的调节中起着核心作用。在这里，我们报告了非编码 RNA（ncRNA）在调节关键细胞因子的蛋白质动力学中的作用，包括 VHL、Hsp70 和 MDM2/PML。核仁基因间间隔区的刺激特异性位点产生能够捕获和固定蛋白质的 ncRNA，这些蛋白质编码一种离散的肽码，称为核仁拘留序列（NoDS）。NoDS/基因间 RNA 相互作用的破坏使蛋白质能够逃避核仁隔离并保持其动态特征。基因间 ncRNA 的定位错误会触发蛋白质在核仁外的固定，这表明这些 ncRNA 可以独立于核仁结构发挥作用。我们提出了一个模型，即 ncRNA 通过蛋白质固定是一种翻译后调节机制。
