Li Jia, Bai Ruoling, Zhou Yulian, Song Xu, Li Ling
Center for Functional Genomics and Bioinformatics, Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, China.
PLoS Genet. 2025 Jan 27;21(1):e1011580. doi: 10.1371/journal.pgen.1011580. eCollection 2025 Jan.
A bidirectional nucleus-mitochondria communication is essential for homeostasis and stress. By acting as critical molecules, the nuclear-encoded lncRNAs (nulncRNAs) have been implicated in the nucleus-to-mitochondria anterograde regulation. However, role of mitochondrial-derived lncRNAs (mtlncRNAs) in the mitochondria-to-nucleus retrograde regulation remains elusive. Here, we identify functional implication of the mtlncRNAs MDL1AS, lncND5 and lncCyt b in retrograde regulation. Mediated by HuR and PNPT1 proteins, the mtlncRNAs undergo a mitochondria-to-nucleus traveling and then regulate a network of nuclear genes. Moreover, as an example of the functional consequence, we showed that the nuclear-translocated lncCyt b cooperates with the splicing factor hnRNPA2B1 to influence several aspects of cell metabolism including glycolysis, possibly through their regulatory effect on the post-transcriptional processing of related nuclear genes. This study advances our knowledge in mitochondrial biology and provides new insights into the role of mtlncRNAs in mitochondria-nucleus communications.
细胞核与线粒体之间的双向通讯对于体内平衡和应激反应至关重要。作为关键分子，核编码的长链非编码RNA（nulncRNAs）参与了从细胞核到线粒体的正向调控。然而，线粒体衍生的长链非编码RNA（mtlncRNAs）在线粒体到细胞核的逆向调控中的作用仍不清楚。在这里，我们确定了mtlncRNAs MDL1AS、lncND5和lncCyt b在逆向调控中的功能意义。在HuR和PNPT1蛋白的介导下，mtlncRNAs经历从线粒体到细胞核的转运，然后调控一个核基因网络。此外，作为功能后果的一个例子，我们表明核转位的lncCyt b与剪接因子hnRNPA2B1协同作用，可能通过它们对相关核基因转录后加工的调节作用，影响细胞代谢的几个方面，包括糖酵解。这项研究增进了我们对线粒体生物学的了解，并为mtlncRNAs在线粒体-细胞核通讯中的作用提供了新的见解。
