RPUSD4, an uncharacterized mitochondrial putative pseudouridine synthase, is essential for mitochondrial function. It is involved in pathways such as oxidative phosphorylation and mitochondrial gene expression, playing a crucial role in maintaining normal cellular energy metabolism and mitochondrial translation [1,2,3]. Genetic models, especially gene knockout models, are valuable for further exploring its functions.

Depletion of RPUSD4 leads to a severe reduction of the steady-state level of the 16S mitochondrial (mt) rRNA, defects in the biogenesis of the mitoribosome large subunit, and consequently in mitochondrial translation. RPUSD4 binds 16S mt-rRNA, mt-tRNAMet, and mt-tRNAPhe, and is responsible for pseudouridylation of the latter. Also, it is part of a protein module in mitochondrial RNA granules essential for mitochondrial protein synthesis and cell viability, and its depletion causes specific mitochondrial protein synthesis and oxidative phosphorylation assembly defects without affecting mitochondrial mRNA levels [2,3].

In conclusion, RPUSD4 is essential for mitochondrial gene expression, specifically in the processes of rRNA stability, mitoribosome assembly, and mitochondrial translation. Through studies using gene-knockout models, its role in maintaining normal mitochondrial function and thus in processes like oxidative phosphorylation has been revealed. Understanding RPUSD4 can provide insights into mitochondrial-related diseases and cellular energy metabolism disorders.