Rbm33-flox Mouse

Rbm33, an RNA-binding protein, has multiple crucial functions. It is involved in regulating the RNA substrate selectivity of m6A demethylase ALKBH5, and also directs the nuclear export of transcripts containing GC-rich elements [1,2]. In terms of associated pathways, it is linked to autophagy regulation and tumorigenesis, especially in head-neck squamous cell carcinoma (HNSCC), and it may be involved in pathways related to extracellular matrix degradation in abdominal aortic aneurysm (AAA) [1,3].

In a KO mouse model study, hippocampus-specific genetic deletion of RBM33 alleviated age-related declines in learning and memory in aged RBM33 knockout (RBM33-/-) mice, while hippocampus-specific overexpression of RBM33 exacerbated these declines in aged RBM33 overexpression (RBM33Tg) mice. This indicates that RBM33 acts as an age-promoting factor in the hippocampus, likely through its liquid-liquid phase separation (LLPS) which is required for its binding to the CDKN1A (p21cip1) promoter, inducing microglial senescence [4].

In conclusion, Rbm33 plays important roles in processes like m6A-mediated mRNA regulation, nuclear export of specific transcripts, tumorigenesis, and hippocampal aging. The Rbm33 KO/overexpression mouse models have revealed its function in hippocampal-dependent cognitive decline, providing insights into potential therapeutic strategies for age-related neurodegenerative diseases.