Luc7l2 is a gene encoding a protein that may be involved in the recognition of non-consensus splice donor sites in association with the U1 snRNP spliceosomal subunit [3]. It plays important roles in multiple biological processes, such as energy metabolism regulation, innate immune response, and DNA damage repair. It is also associated with various diseases including glioblastoma, liver cancer, chordoma, nasopharyngeal carcinoma, and myeloid neoplasms [1,3,4,6,8-10].

In glioblastoma, histone H3K9 lactylation activates LUC7L2 transcription. LUC7L2 then mediates intron 7 retention of MLH1, reducing MLH1 expression and inhibiting mismatch repair, leading to temozolomide resistance [1]. In liver cancer cells, LUC7L2 promotes proliferation and enhances DNA damage repair via RRAS [3]. In nasopharyngeal carcinoma, overexpression of LUC7L2 promotes radioresistance via autophagy, while knockdown sensitizes radio-resistant cells [5]. LUC7L2-deficient mice exhibit resistance to lethal herpes simplex virus 1 infection, as LUC7L2 negatively regulates the innate antiviral response by mediating MITA/STING intron retention [4]. Loss of LUC7L2 in cells shifts energy metabolism from glycolysis to oxidative phosphorylation (OXPHOS) through multiple splicing-related mechanisms [2].

In summary, Luc7l2 is a key gene involved in splicing regulation, which impacts diverse biological processes and disease-related pathways. The use of gene knockout or conditional knockout models, like the LUC7L2-deficient mice, has been crucial in revealing its role in diseases such as glioblastoma, liver cancer, nasopharyngeal carcinoma, and in antiviral immune response, providing insights into potential therapeutic strategies for these conditions.

References:

1. Yue, Qu, Wang, Zhao, Shen, Yixiong, Liu, Boyang, Guo, Hongbo. 2024. Histone H3K9 Lactylation Confers Temozolomide Resistance in Glioblastoma via LUC7L2-Mediated MLH1 Intron Retention. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2309290. doi:10.1002/advs.202309290. https://pubmed.ncbi.nlm.nih.gov/38477507/

2. Jourdain, Alexis A, Begg, Bridget E, Mick, Eran, Burge, Christopher B, Mootha, Vamsi K. 2021. Loss of LUC7L2 and U1 snRNP subunits shifts energy metabolism from glycolysis to OXPHOS. In Molecular cell, 81, 1905-1919.e12. doi:10.1016/j.molcel.2021.02.033. https://pubmed.ncbi.nlm.nih.gov/33852893/

3. Liu, Xinlei, Xie, Sijie, Jiang, Xiaoxue, Li, Shujie, Lu, Dongdong. 2024. LUC7L2 accelerates the growth of liver cancer cells by enhancing DNA damage repair via RRAS. In Cells & development, 180, 203976. doi:10.1016/j.cdev.2024.203976. https://pubmed.ncbi.nlm.nih.gov/39571735/

4. Li, Chen, Feng, Lu, Luo, Wei-Wei, Li, Mi, Shu, Hong-Bing. 2021. The RNA-binding protein LUC7L2 mediates MITA/STING intron retention to negatively regulate innate antiviral response. In Cell discovery, 7, 46. doi:10.1038/s41421-021-00277-y. https://pubmed.ncbi.nlm.nih.gov/34155193/

5. Shen, Lin, Li, Chao, Chen, Fang, Li, Zhanzhan, Li, Na. 2021. CRISPR/Cas9 genome-wide screening identifies LUC7L2 that promotes radioresistance via autophagy in nasopharyngeal carcinoma cells. In Cell death discovery, 7, 392. doi:10.1038/s41420-021-00783-8. https://pubmed.ncbi.nlm.nih.gov/34907164/