Lsm14a-KO Mouse

Lsm14a, a member of the LSm family, is involved in RNA processing within messenger RNA processing bodies (P-bodies) in the cytoplasm [3,4,6,7,8]. It plays crucial roles in various biological processes, including the initiation of the cellular antiviral response. It binds to viral nucleic acids, mediates IRF3 activation and IFN-β induction, and thus is important for innate antiviral immunity [7].

In glioblastoma (GBM), overexpression of Lsm14A is associated with poorer prognosis. Functional assays in vitro and in vivo mouse xenograft models showed that Lsm14A promotes GBM cell proliferation, migration, and invasion. Mechanistically, during the G1/S phase, it stabilizes DDX5 in the cytoplasm, regulating CDK4 and P21 levels, and METTL1 modulates its expression via mRNA m7G methylation [1]. In a case of extraskeletal myxoid chondrosarcoma, a novel fusion transcript LSM14A::NR4A3 was identified, expanding the molecular spectrum of this disease [2]. In the context of porcine reproductive and respiratory syndrome virus (PRRSV), overexpression of porcine LSM14A inhibits PRRSV replication in Marc-145 cells and porcine alveolar macrophages by activating the IFN-β signaling pathway, while knockdown enhances replication [5].

In summary, Lsm14a has diverse functions, particularly in antiviral immune responses and in the context of certain cancers. The findings from in vitro and in vivo models, such as the mouse xenograft model in GBM research, have revealed its role in disease-related biological processes, offering potential therapeutic targets for diseases like GBM and new insights into understanding the molecular mechanisms of diseases like extraskeletal myxoid chondrosarcoma and PRRSV-related diseases [1,2,5].

References:

1. Wang, Changyu, He, Yan, Fang, Xiang, Li, Lun, Li, Guangyu. 2024. METTL1-modulated LSM14A facilitates proliferation and migration in glioblastoma via the stabilization of DDX5. In iScience, 27, 110225. doi:10.1016/j.isci.2024.110225. https://pubmed.ncbi.nlm.nih.gov/39040050/

2. Ngo, Carine, Verret, Benjamin, Vibert, Julien, Scoazec, Jean-Yves, Pierron, Gaëlle. 2022. A novel fusion variant LSM14A::NR4A3 in extraskeletal myxoid chondrosarcoma. In Genes, chromosomes & cancer, 62, 52-56. doi:10.1002/gcc.23090. https://pubmed.ncbi.nlm.nih.gov/35932215/

3. Bloch, Donald B, Sinow, Claire O, Sauer, Andrew J, Corman, Benjamin H P. 2023. Assembly and regulation of the mammalian mRNA processing body. In PloS one, 18, e0282496. doi:10.1371/journal.pone.0282496. https://pubmed.ncbi.nlm.nih.gov/36877681/

4. Zhan, Wanqi, Li, Zhiyang, Zhang, Jie, Chen, Wankun, Wang, Zhizhang. 2024. Energy stress promotes P-bodies formation via lysine-63-linked polyubiquitination of HAX1. In The EMBO journal, 43, 2759-2788. doi:10.1038/s44318-024-00120-6. https://pubmed.ncbi.nlm.nih.gov/38769438/

5. Li, Zhenhong, Chen, Rui, Zhao, Jinhua, Zhen, Yueran, Liu, Bang. 2014. LSM14A inhibits porcine reproductive and respiratory syndrome virus (PRRSV) replication by activating IFN-β signaling pathway in Marc-145. In Molecular and cellular biochemistry, 399, 247-56. doi:10.1007/s11010-014-2251-8. https://pubmed.ncbi.nlm.nih.gov/25408553/

6. Shen, Xia, Peng, Xiang, Guo, YueGui, Liu, Yun, Liu, Chen-Ying. 2024. YAP/TAZ enhances P-body formation to promote tumorigenesis. In eLife, 12, . doi:10.7554/eLife.88573. https://pubmed.ncbi.nlm.nih.gov/39046443/

7. Li, Ying, Chen, Rui, Zhou, Qian, He, Weiwu, Shu, Hong-Bing. 2012. LSm14A is a processing body-associated sensor of viral nucleic acids that initiates cellular antiviral response in the early phase of viral infection. In Proceedings of the National Academy of Sciences of the United States of America, 109, 11770-5. doi:10.1073/pnas.1203405109. https://pubmed.ncbi.nlm.nih.gov/22745163/

8. Hua, Kexin, Li, Huilin, Chen, Huanchun, Luo, Rui, Jin, Hui. 2017. Functional characterization of duck LSm14A in IFN-β induction. In Developmental and comparative immunology, 76, 255-261. doi:10.1016/j.dci.2017.06.014. https://pubmed.ncbi.nlm.nih.gov/28666650/