Zhang Xiaqing, Guo Jing, Shi Xin, Zhou Xin, Chen Qiang
Department of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China.
Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, 430071, China.
Cell Insight. 2024 Mar 23;3(3):100170. doi: 10.1016/j.cellin.2024.100170. eCollection 2024 Jun.
The RNA-binding protein LUC7L3 is the human homolog of yeast U1 small nuclear RNA (snRNA)-related splicing factor Luc7p. While the primary function of LUC7L3 as an RNA-binding protein is believed to be involved in RNA metabolism, particularly in the splicing process, its exact role and other functions are still not fully understood. In this study, we aimed to elucidate the role of LUC7L3 and its impact on cell proliferation. Our study revealed that LUC7L3 depletion impairs cell proliferation compared to the other Luc7p paralogs, resulting in cell apoptosis and senescence. We explored the underlying mechanisms and found that LUC7L3 depletion leads to R-loop accumulation, DNA replication stress, and genome instability. Furthermore, we discovered that LUC7L3 depletion caused abnormalities in spindle assembly, leading to the formation of multinuclear cells. This was attributed to the dysregulation of protein translation of spindle-associated proteins. Additionally, we investigated the interplay between LUC7L3 and SRSF1 and identified SRSF1 as an upper stream regulator of LUC7L3, promoting the translation of LUC7L3 protein. These findings highlight the importance of LUC7L3 in maintaining genome stability and its relationship with SRSF1 in this regulatory pathway.
RNA结合蛋白LUC7L3是酵母U1小核RNA（snRNA）相关剪接因子Luc7p的人类同源物。虽然LUC7L3作为一种RNA结合蛋白的主要功能被认为参与RNA代谢，特别是在剪接过程中，但其确切作用和其他功能仍未完全了解。在本研究中，我们旨在阐明LUC7L3的作用及其对细胞增殖的影响。我们的研究表明，与其他Luc7p旁系同源物相比，LUC7L3的缺失会损害细胞增殖，导致细胞凋亡和衰老。我们探究了其潜在机制，发现LUC7L3的缺失会导致R环积累、DNA复制应激和基因组不稳定。此外，我们发现LUC7L3的缺失会导致纺锤体组装异常，导致多核细胞的形成。这归因于纺锤体相关蛋白的蛋白质翻译失调。此外，我们研究了LUC7L3与SRSF1之间的相互作用，并确定SRSF1是LUC7L3的上游调节因子，促进LUC7L3蛋白的翻译。这些发现突出了LUC7L3在维持基因组稳定性中的重要性及其在该调节途径中与SRSF1的关系。
