Feng Xi, Wang Xiaoman, Guang Shouhong, Pang Shanshan, Tang Haiqing
School of Life Sciences, Chongqing University, Chongqing, China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, The USTC RNA Institute, Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, School of Life Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China, Hefei, China.
PLoS Biol. 2025 May 21;23(5):e3003190. doi: 10.1371/journal.pbio.3003190. eCollection 2025 May.
In response to nutrient scarcity, cells must reallocate their limited energy for cellular maintenance at the expense of certain processes. How such a tradeoff is achieved remains largely unknown. RNA surveillance is crucial for the integrity of the transcriptome, whose defects are associated with several human diseases. Unexpectedly, we discover that the nucleolar RNA exosome, a key RNA surveillance machine, is inhibited by starvation. This is not merely the cessation of a temporarily non-essential process, but rather a key signal to allocate energy. By rewiring one-carbon metabolism, the inhibition of RNA exosome reduces translation, the most energy-consuming process. Energy is then conserved for fat synthesis to enhance cellular maintenance and starvation survival. Notably, while benefiting starvation fitness, RNA exosome inhibition impairs the life span of well-fed animals, indicating a tradeoff between short-term and long-term fitness. Our findings suggest that the nucleolar RNA surveillance can be temporarily sacrificed to facilitate starvation adaptation.
为应对营养物质短缺，细胞必须以牺牲某些过程为代价，重新分配其有限的能量用于细胞维持。目前尚不清楚这种权衡是如何实现的。RNA监测对于转录组的完整性至关重要，转录组缺陷与多种人类疾病相关。出乎意料的是，我们发现核仁RNA外切体，一种关键的RNA监测机器，会受到饥饿的抑制。这不仅仅是一个暂时非必需过程的停止，更是一个分配能量的关键信号。通过重新连接一碳代谢，RNA外切体的抑制减少了翻译，这是最耗能的过程。然后能量被保存用于脂肪合成，以增强细胞维持和饥饿生存能力。值得注意的是，虽然RNA外切体抑制有利于饥饿适应，但会损害营养充足动物的寿命，这表明短期和长期适应性之间存在权衡。我们的研究结果表明，可以暂时牺牲核仁RNA监测来促进饥饿适应。
