Mitochondrial tRNA Pseudouridylation Regulates Erythropoiesis Via the mTOR Signaling Pathway: Implications for Mlasa and Treatment Strategies

Pseudouridine, the most abundant RNA modification found in various RNA molecules, is crucial for cellular functions. Pseudouridylation is the process of converting uridine to pseudouridine, catalyzed by pseudouridine synthases (PUSs), and abnormal pseudouridylation has been linked to human diseases, including mitochondrial myopathy, lactic acidosis, and sideroblastic anemia syndrome (MLASA). MLASA is associated with genetic mutations in the PUS1 gene, leading to progressive exercise intolerance, sideroblastic anemia, hyperlactatemia, and muscle weakness. The underlying mechanism of anemia in MLASA remains unclear.