美国丹娜-法伯癌症研究所Bruce M. Spiegelman研究小组发现，RBM43控制PGC1α翻译和PGC1α- STING信号轴。2025年2月17日出版的《细胞—代谢》杂志发表了这一最新研究成果。

研究小组发现PGC1α是线粒体生物发生的关键调控因子，在mRNA翻译水平上受到RNA结合蛋白RBM43的负调控。RBM43受炎症细胞因子诱导，并以依赖于PGC1α的方式抑制线粒体的生物发生。在小鼠中，脂肪细胞选择性Rbm43破坏可提高PGC1α翻译和氧化代谢。在肥胖中，Rbm43的缺失改善了葡萄糖耐量，减少了脂肪炎症，抑制了脂肪细胞中先天免疫传感器cGAS-STING的激活。

小组进一步确定了PGC1α在防止线粒体DNA（一种cGAS配体）的细胞质积累中的作用。RBM43的作用定义了一个翻译调节轴，炎症信号通过该轴指示细胞能量代谢并参与代谢性疾病的发病机制。

据悉，肥胖与损害线粒体功能的全身性炎症有关。这种破坏减少了氧化代谢，限制了脂肪细胞脂质代谢和产热，这是一种代谢有益的程序，可以将化学能转化为热量。

附：英文原文

Title: RBM43 controls PGC1α translation and a PGC1α-STING signaling axis

Author: Phillip A. Dumesic, Sarah E. Wilensky, Symanthika Bose, Jonathan G. Van Vranken, Steven P. Gygi, Bruce M. Spiegelman

Issue&Volume: 2025-02-17

Abstract: Obesity is associated with systemic inflammation that impairs mitochondrial function. This disruption curtails oxidative metabolism, limiting adipocyte lipid metabolism and thermogenesis, a metabolically beneficial program that dissipates chemical energy as heat. Here, we show that PGC1α, a key governor of mitochondrial biogenesis, is negatively regulated at the level of its mRNA translation by the RNA-binding protein RBM43. RBM43 is induced by inflammatory cytokines and suppresses mitochondrial biogenesis in a PGC1α-dependent manner. In mice, adipocyte-selective Rbm43 disruption elevates PGC1α translation and oxidative metabolism. In obesity, Rbm43 loss improves glucose tolerance, reduces adipose inflammation, and suppresses activation of the innate immune sensor cGAS-STING in adipocytes. We further identify a role for PGC1α in safeguarding against cytoplasmic accumulation of mitochondrial DNA, a cGAS ligand. The action of RBM43 defines a translational regulatory axis by which inflammatory signals dictate cellular energy metabolism and contribute to metabolic disease pathogenesis.

DOI: 10.1016/j.cmet.2025.01.013

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00013-0