Beaupere Carine, Wasko Brian M, Lorusso Jared, Kennedy Brian K, Kaeberlein Matt, Labunskyy Vyacheslav M
Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA.
Department of Pathology, University of Washington, Seattle, WA 98195, USA.
Cell Rep. 2017 Feb 21;18(8):1884-1892. doi: 10.1016/j.celrep.2017.01.077.
Transcriptional regulation plays an important role in the control of gene expression during aging. However, translation efficiency likely plays an equally important role in determining protein abundance, but it has been relatively understudied in this context. Here, we used RNA sequencing (RNA-seq) and ribosome profiling to investigate the role of translational regulation in lifespan extension by CAN1 gene deletion in yeast. Through comparison of the transcriptional and translational changes in cells lacking CAN1 with other long-lived mutants, we were able to identify critical regulatory factors, including transcription factors and mRNA-binding proteins, that coordinate transcriptional and translational responses. Together, our data support a model in which deletion of CAN1 extends replicative lifespan through increased translation of proteins that facilitate cellular response to stress. This study extends our understanding of the importance of translational control in regulating stress resistance and longevity.
转录调控在衰老过程中基因表达的控制中起着重要作用。然而,翻译效率在决定蛋白质丰度方面可能同样起着重要作用,但在这种情况下,对其研究相对较少。在这里,我们使用RNA测序(RNA-seq)和核糖体分析来研究酵母中CAN1基因缺失导致寿命延长过程中翻译调控的作用。通过比较缺乏CAN1的细胞与其他长寿突变体的转录和翻译变化,我们能够鉴定出关键的调控因子,包括转录因子和mRNA结合蛋白,它们协调转录和翻译反应。总之,我们的数据支持这样一个模型,即CAN1的缺失通过增加有助于细胞应激反应的蛋白质的翻译来延长复制寿命。这项研究扩展了我们对翻译控制在调节抗逆性和寿命方面重要性的理解。