Matr3, also known as Matrin-3, is a nuclear matrix protein with multifaceted functions. It is involved in regulating gene expression at multiple levels, including chromatin organization, DNA transcription, RNA metabolism, and protein translation in both the nucleus and cytoplasm. Matr3 may play a critical role in various cellular processes such as DNA damage response, cell proliferation, differentiation, and survival [2].

In liver cancer, MATR3 expression is upregulated, promoting cell proliferation and metastasis. It downregulates the type I IFN signaling pathway by binding to DHX58 mRNA via its RRM domain, recruiting YTHDF2, and degrading DHX58 mRNA. Knocking out MATR3 in liver cancer cells triggers a natural immune response, stimulating CD8+ T cells to eliminate the cancer cells [1]. In FSHD muscular dystrophy, MATR3 binds to the DUX4 DNA-binding domain, blocking DUX4-mediated gene expression and rescuing cell viability and myogenic differentiation of FSHD muscle cells [3]. Loss of MATR3 leads to cryptic exon inclusion in many transcripts, and disease-associated variants like the ALS-linked S85C and the novel neurodevelopmental disease-associated M548T variant differentially impair its cryptic splicing repression function [4].

In conclusion, Matr3 is a key regulator in gene expression and cellular processes. Studies using gene knockout or knockdown models have revealed its significant roles in diseases such as liver cancer, FSHD muscular dystrophy, and neurodegenerative/neurodevelopmental diseases. Understanding Matr3's functions through these models provides insights into disease mechanisms and potential therapeutic targets.