Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
Nat Commun. 2017 Mar 9;8:14749. doi: 10.1038/ncomms14749.
Long-lived organisms often feature more stringent protein and DNA quality control. However, whether RNA quality control mechanisms, such as nonsense-mediated mRNA decay (NMD), which degrades both abnormal as well as some normal transcripts, have a role in organismal aging remains unexplored. Here we show that NMD mediates longevity in C. elegans strains with mutations in daf-2/insulin/insulin-like growth factor 1 receptor. We find that daf-2 mutants display enhanced NMD activity and reduced levels of potentially aberrant transcripts. NMD components, including smg-2/UPF1, are required to achieve the longevity of several long-lived mutants, including daf-2 mutant worms. NMD in the nervous system of the animals is particularly important for RNA quality control to promote longevity. Furthermore, we find that downregulation of yars-2/tyrosyl-tRNA synthetase, an NMD target transcript, by daf-2 mutations contributes to longevity. We propose that NMD-mediated RNA surveillance is a crucial quality control process that contributes to longevity conferred by daf-2 mutations.
长寿生物通常具有更严格的蛋白质和 DNA 质量控制。然而，RNA 质量控制机制（如无意义介导的 mRNA 降解（NMD），它降解异常和一些正常转录本）是否在机体衰老中起作用仍未被探索。在这里，我们表明 NMD 介导了具有 daf-2/胰岛素/胰岛素样生长因子 1 受体突变的 C. elegans 品系的长寿。我们发现，daf-2 突变体显示出增强的 NMD 活性和降低的潜在异常转录本水平。包括 smg-2/UPF1 在内的 NMD 成分对于实现包括 daf-2 突变体蠕虫在内的几种长寿命突变体的长寿是必需的。动物神经系统中的 NMD 对于促进长寿的 RNA 质量控制尤为重要。此外，我们发现，daf-2 突变导致 NMD 靶转录本 yars-2/酪氨酸-tRNA 合成酶的下调有助于长寿。我们提出，NMD 介导的 RNA 监测是一种至关重要的质量控制过程，有助于 daf-2 突变赋予的长寿。
