Matr3-KO Mouse

Matr3, also known as Matrin-3, is a nuclear matrix protein. It is involved in multiple crucial biological processes, regulating gene expression at various levels such as chromatin organization, DNA transcription, RNA metabolism, and protein translation [3]. It also participates in cellular processes like DNA damage response, cell proliferation, differentiation, and survival [3].

In liver cancer, Matr3 promotes cancer progression. It upregulates its expression, correlating with poor prognosis. Matr3 binds to DHX58 mRNA, recruits YTHDF2, degrades DHX58 mRNA, and suppresses the type I IFN signaling pathway. Knocking out Matr3 in liver cancer cells triggers a natural immune response, stimulating CD8+ T cells to eliminate cancer cells [1].

In the context of chromatin organization, Matr3 and antisense LINE1 (AS L1) RNAs form a meshwork via phase separation, which scaffolds higher-order chromatin organization. Depletion of Matr3 leads to chromatin redistribution and altered intra-TAD interactions [2].

Regarding neurodegenerative diseases, many missense mutations in Matr3 have been linked to familial forms of amyotrophic lateral sclerosis (ALS) and distal myopathy. However, MATR3 P154S knock-in mice did not develop progressive motor deficits or ALS-like pathology, suggesting this variant is not sufficient to produce ALS-like pathology in vivo [4].

In summary, Matr3 is essential for regulating gene expression and various cellular functions. Studies using gene knockout and knock-in mouse models have provided insights into its role in liver cancer progression and its potential link to neurodegenerative diseases such as ALS. These model-based studies contribute to a better understanding of the biological functions of Matr3 and its implications in disease mechanisms [1,2,4].

References:

1. Xiao, Zhaofeng, Chen, Huan, Xu, Nan, Wang, Shuai, Xu, Xiao. 2024. MATR3 promotes liver cancer progression by suppressing DHX58-mediated type I interferon response. In Cancer letters, 604, 217231. doi:10.1016/j.canlet.2024.217231. https://pubmed.ncbi.nlm.nih.gov/39276912/

2. Zhang, Yuwen, Cao, Xuan, Gao, Zehua, Wei, Gang, Wen, Bo. 2023. MATR3-antisense LINE1 RNA meshwork scaffolds higher-order chromatin organization. In EMBO reports, 24, e57550. doi:10.15252/embr.202357550. https://pubmed.ncbi.nlm.nih.gov/37381832/

3. Santos, Jhune Rizsan, Park, Jeehye. 2024. MATR3's Role beyond the Nuclear Matrix: From Gene Regulation to Its Implications in Amyotrophic Lateral Sclerosis and Other Diseases. In Cells, 13, . doi:10.3390/cells13110980. https://pubmed.ncbi.nlm.nih.gov/38891112/

4. Dominick, Marissa, Houchins, Nicole, Venugopal, Vinisha, Bowser, Robert, Medina, David X. 2023. MATR3 P154S knock-in mice do not exhibit motor, muscle or neuropathologic features of ALS. In Biochemical and biophysical research communications, 645, 164-172. doi:10.1016/j.bbrc.2023.01.032. https://pubmed.ncbi.nlm.nih.gov/36689813/