Trub2, a member of the human TruB family of pseudouridine synthase genes, is mainly located in mitochondria [5]. It plays a crucial role in mitochondrial function, being involved in mitochondrial RNA modification, specifically in the pseudouridylation of mitochondrial mRNAs [4]. This process is essential for mitochondrial protein synthesis, oxidative phosphorylation, and ultimately cell viability [4]. It is part of a functional module that regulates mitochondrial 16S rRNA and intra-mitochondrial translation, along with genes like NGRN, WBSCR16, RPUSD3, RPUSD4, and FASTKD2, which is vital for the major ATP-producing pathway of oxidative phosphorylation in humans [1].

Depletion of TRUB2 leads to specific mitochondrial protein synthesis and oxidative phosphorylation assembly defects without affecting mitochondrial mRNA levels [4]. In the context of diseases, in renal clear-cell carcinoma and papillary-cell carcinoma, the prognostic value of TRUB2 is being investigated [2]. In lower grade glioma, a mitochondrial RNA modification-based signature including TRUB2 was established to predict prognosis, malignant clinical characteristics, immune infiltration, gene variation, and response to therapies [3]. In metabolic dysfunction-associated steatotic liver disease (MASLD), inhibition of Trub2 increased intracellular triglyceride levels in AML12 cells, and betaine was found to reduce these levels by increasing Trub2 expression, suggesting a potential target for MASLD treatment [6].

In summary, Trub2 is essential for mitochondrial protein synthesis and oxidative phosphorylation through its role in mitochondrial RNA pseudouridylation. Research on Trub2 using genetic models has provided insights into its functions in various disease conditions such as renal carcinomas, lower grade glioma, and MASLD, highlighting its potential as a therapeutic target.