LUC7L3 is a downstream factor of SRSF1 and prevents genomic instability
Xiaqing Zhang,
Jing Guo,
Xin Shi,
Xin Zhou,
Qiang Chen
Affiliations
Xiaqing Zhang
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
Jing Guo
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
Xin Shi
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
Xin Zhou
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
Qiang Chen
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; Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Wuhan, 430071, China; Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China; Hubei Province Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China; Corresponding author. Department of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China.
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.
