Pus1-flox Mouse

PUS1, encoding the nuclear PUS1 enzyme, is located in both the nucleus and the mitochondria. It belongs to the family of PUS enzymes that participate in RNA modifications, converting uridine into pseudouridine in several cytosolic and mitochondrial transfer RNA positions, thus increasing the efficiency of protein synthesis in both compartments. PUS1 is involved in various biological processes and has been linked to important pathways like those related to cell proliferation, migration, and translation of oncogenic mRNAs [2,3,4,6].

In prostate cancer, knockdown of PUS1 inhibited bone metastasis independently of its enzymatic activity, with EIF3b as a downstream effector protected from ubiquitin-mediated degradation by PUS1 [1]. In hepatocellular carcinoma, PUS1 overexpression promoted cell proliferation and tumor growth, and knockdown had the opposite effects. PUS1 incorporated pseudouridine into mRNAs of oncogenes, enhancing their translation [6]. In breast cancer, high PUS1 levels were associated with poor outcomes and triple-negative status, and knockdown suppressed cell proliferation, colony formation, and invasion [5]. In non-small cell lung cancer (NSCLC), high PUS1 expression was associated with shorter survival, and it may be involved in NSCLC malignancy and immune cell infiltration [7]. In MLASA syndrome, mutations in PUS1 led to impaired erythropoiesis, anemia, and compromised mitochondrial function [8].

In conclusion, PUS1 plays crucial roles in RNA modification and protein synthesis, affecting various biological processes. Through gene knockout or knockdown studies in different disease models, it has been shown to be involved in cancer progression, such as in prostate, liver, breast, and lung cancers, as well as in the pathogenesis of MLASA syndrome. These findings highlight its potential as a biomarker and therapeutic target in related diseases.