Pus7-flox Mouse

PUS7, or Pseudouridine Synthase 7, is an enzyme crucial for pseudouridylation, the most frequent epitranscriptomic modification. It impacts various biological functions by modifying RNAs, influencing processes like translation and gene expression [1,2,4,6].

In glioblastoma, high PUS7 expression is associated with poor survival, and its expression and catalytic activity are required for glioblastoma stem cell tumorigenesis. PUS7-mediated tRNA pseudouridylation controls codon-specific translation of key GSC regulators, and chemical inhibitors of PUS7 can suppress tumorigenesis [1].

In gastric cancer, PUS7 is reduced in tumor tissues compared to non-tumor tissues. It inhibits gastric cancer cell proliferation and tumour growth by enhancing the translation efficiency of ALKBH3 mRNA through pseudouridylation [2].

In colorectal cancer, PUS7 is highly expressed, promoting cell proliferation by stabilizing SIRT1 to activate the Wnt/β -catenin pathway, and its knockdown suppresses cell proliferation in vitro and tumorigenicity in vivo [3].

In patients with loss-of-function variants in PUS7, a neurodevelopmental phenotype including autism spectrum disorder is observed, along with upregulated protein synthesis in patient fibroblasts [5].

Overall, PUS7 plays a significant role in multiple biological processes and diseases. Its function in translation regulation and disease-related phenotypes, as revealed through studies on gene-modified models and patient samples, highlights its potential as a therapeutic target in cancers like glioblastoma, gastric cancer, and colorectal cancer, as well as its importance in understanding neurodevelopmental disorders [1-3,6].