Rpusd4-KO Mouse

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RPUSD4, an uncharacterized mitochondrial putative pseudouridine synthase, is essential for mitochondrial function. It is part of a functional module regulating mitochondrial 16S rRNA and intra-mitochondrial translation, and is involved in RNA post-transcriptional modification within mitochondrial RNA granules (MRGs) [1,2,3,4]. It plays a role in pathways related to oxidative phosphorylation and mitochondrial protein synthesis, which are crucial for cell viability [1,3]. Genetic models, such as KO mouse models, could potentially be valuable in further exploring its function.

Depletion of RPUSD4 leads to a severe reduction in the steady-state level of the 16S mitochondrial (mt) rRNA, defects in mitoribosome large subunit biogenesis and mitochondrial translation. RPUSD4 binds 16S mt-rRNA, mt-tRNAMet, and mt-tRNAPhe, and is responsible for the pseudouridylation of the latter. It also plays a role in the pseudouridylation of a single residue in the 16S rRNA, which is essential for its stability and assembly into the mitochondrial ribosome [2,3]. In addition, in osteoarthritis, RPUSD4 was found to be expressed at low levels compared to healthy samples [5].

In conclusion, RPUSD4 is vital for mitochondrial gene expression through its role in RNA pseudouridylation, which impacts mitochondrial ribosome assembly, translation, and oxidative phosphorylation. Its dysregulation is associated with conditions like osteoarthritis. Studies using KO/CKO mouse models could further clarify its role in these biological processes and disease conditions, providing insights into potential therapeutic targets.