Wei Yu-Ning, Hu Hai-Yang, Xie Gang-Cai, Fu Ning, Ning Zhi-Bin, Zeng Rong, Khaitovich Philipp
Genome Biol. 2015 Feb 22;16(1):41. doi: 10.1186/s13059-015-0608-2.
In studies of development and aging, the expression of many genes has been shown to undergo drastic changes at mRNA and protein levels. The connection between mRNA and protein expression level changes, as well as the role of posttranscriptional regulation in controlling expression level changes in postnatal development and aging, remains largely unexplored.
Here, we survey mRNA and protein expression changes in the prefrontal cortex of humans and rhesus macaques over developmental and aging intervals of both species' lifespans. We find substantial decoupling of mRNA and protein expression levels in aging, but not in development. Genes showing increased mRNA/protein disparity in primate brain aging form expression patterns conserved between humans and macaques and are enriched in specific functions involving mammalian target of rapamycin (mTOR) signaling, mitochondrial function and neurodegeneration. Mechanistically, aging-dependent mRNA/protein expression decoupling could be linked to a specific set of RNA binding proteins and, to a lesser extent, to specific microRNAs.
Increased decoupling of mRNA and protein expression profiles observed in human and macaque brain aging results in specific co-expression profiles composed of genes with shared functions and shared regulatory signals linked to specific posttranscriptional regulators. Genes targeted and predicted to be targeted by the aging-dependent posttranscriptional regulation are associated with biological processes known to play important roles in aging and lifespan extension. These results indicate the potential importance of posttranscriptional regulation in modulating aging-dependent changes in humans and other species.
在发育和衰老研究中，许多基因的表达已被证明在mRNA和蛋白质水平上会发生剧烈变化。mRNA与蛋白质表达水平变化之间的联系，以及转录后调控在控制出生后发育和衰老过程中表达水平变化的作用，在很大程度上仍未得到探索。
在这里，我们研究了人类和恒河猴前额叶皮层在两个物种寿命的发育和衰老阶段的mRNA和蛋白质表达变化。我们发现在衰老过程中mRNA和蛋白质表达水平存在显著解耦，但在发育过程中没有。在灵长类动物大脑衰老过程中显示出mRNA/蛋白质差异增加的基因形成了人类和猕猴之间保守的表达模式，并且在涉及雷帕霉素哺乳动物靶标（mTOR）信号传导、线粒体功能和神经退行性变的特定功能中富集。从机制上讲，衰老依赖性的mRNA/蛋白质表达解耦可能与一组特定的RNA结合蛋白有关，在较小程度上也与特定的微小RNA有关。
在人类和猕猴大脑衰老过程中观察到的mRNA和蛋白质表达谱的解耦增加导致了由具有共享功能和与特定转录后调节因子相关的共享调节信号的基因组成的特定共表达谱。被衰老依赖性转录后调控靶向和预测靶向的基因与已知在衰老和寿命延长中起重要作用的生物学过程相关。这些结果表明转录后调控在调节人类和其他物种衰老依赖性变化中的潜在重要性。
