Pus7-KO Mouse

Pus7, known as Pseudouridine synthase 7, is an enzyme crucial for pseudouridylation, a post-transcriptional RNA modification. Pseudouridine is the most frequent epitranscriptomic modification, influencing RNA function and gene expression [1,2,5,7,8]. Pus7 is involved in various biological processes such as translational control, especially in stem cells where it modifies tRNA-derived fragments to impact stem cell commitment [5]. It is also associated with multiple disease-related pathways, making it an important target for understanding disease mechanisms.

In glioblastoma, high Pus7 expression is associated with worse patient survival, and its expression and catalytic activity are required for glioblastoma stem cell tumorigenesis. Inhibition of Pus7 suppresses tRNA pseudouridylation, tumorigenesis, and extends the lifespan of tumor-bearing mice [1,4].

In gastric cancer, Pus7 is reduced in tumor tissues. It inhibits gastric cancer cell proliferation and tumor growth by enhancing the translation efficiency of ALKBH3 mRNA through pseudouridylation [2].

In colorectal cancer, Pus7 promotes cell proliferation by directly stabilizing SIRT1 to activate the Wnt/β-catenin pathway [3]. Also, HSP90-dependent Pus7 overexpression facilitates CRC cell metastasis by regulating LASP1 abundance [10].

In human patients, Pus7 deficiency causes a neurodevelopmental phenotype due to dysregulated protein translation [6]. Pan-cancer analysis shows Pus7 is overexpressed in most malignancies, contributing to poor prognosis in several cancer types, and is a potential biomarker and therapeutic target for osteosarcoma [7]. It also affects pre-mRNA processing by co-transcriptional pseudouridylation [8] and is involved in host-SARS-CoV-2 RNA interactions [9].

In conclusion, Pus7 plays essential roles in translational control and is closely associated with various diseases, especially cancer. The use of gene-knockout or conditional-knockout models in research has significantly contributed to understanding how Pus7 functions in disease-related biological processes, providing potential therapeutic strategies for glioblastoma, gastric cancer, colorectal cancer, and other malignancies, as well as insights into neurodevelopmental disorders.