Pus7-KO Mouse

PUS7, or Pseudouridine Synthase 7, is an enzyme crucial for the pseudouridylation process, a key post-transcriptional RNA modification. Pseudouridylation influences gene expression and impacts diverse biological functions, including translational control and RNA processing [1,2,4,5]. It may be involved in multiple pathways, and its dysregulation is linked to various biological conditions.

In glioblastoma, high PUS7 expression is associated with worse patient survival, and its expression and catalytic activity are required for glioblastoma stem cell tumorigenesis. Targeting PUS7 suppresses tRNA pseudouridylation and tumorigenesis, and chemical inhibitors can prevent PUS7-mediated pseudouridine modification, extend the lifespan of tumor-bearing mice [1]. In gastric cancer, PUS7 levels are reduced in tumor tissues compared to non-tumor tissues. PUS7 inhibits gastric cancer cell proliferation and tumour growth via its catalytic activity by enhancing the translation efficiency of ALKBH3 mRNA through pseudouridylation [2]. In colorectal cancer, PUS7 has higher expression in tissues and cell lines. Knockdown of PUS7 suppresses cell proliferation in vitro and inhibits tumorigenicity in vivo. PUS7 promotes cell proliferation by directly stabilizing SIRT1 to activate the Wnt/β-catenin pathway [3].

In summary, PUS7-mediated pseudouridylation plays a significant role in translational control and is involved in the development of multiple cancers such as glioblastoma, gastric cancer, and colorectal cancer. Functional studies, including those using loss-of-function models, have revealed its importance in these disease conditions, providing potential therapeutic targets for cancer treatment [1,2,3].

References:

1. Cui, Qi, Yin, Kailin, Zhang, Xiaoting, Yi, Chengqi, Shi, Yanhong. 2021. Targeting PUS7 suppresses tRNA pseudouridylation and glioblastoma tumorigenesis. In Nature cancer, 2, 932-949. doi:10.1038/s43018-021-00238-0. https://pubmed.ncbi.nlm.nih.gov/35121864/

2. Chang, Yongxia, Jin, Hao, Cui, Yun, Xie, Shanshan, Zhou, Tianhua. . PUS7-dependent pseudouridylation of ALKBH3 mRNA inhibits gastric cancer progression. In Clinical and translational medicine, 14, e1811. doi:10.1002/ctm2.1811. https://pubmed.ncbi.nlm.nih.gov/39175405/

3. Zhang, Qi, Fei, Sujuan, Zhao, Yanchao, Lu, Lili, Chen, Weichang. 2022. PUS7 promotes the proliferation of colorectal cancer cells by directly stabilizing SIRT1 to activate the Wnt/β-catenin pathway. In Molecular carcinogenesis, 62, 160-173. doi:10.1002/mc.23473. https://pubmed.ncbi.nlm.nih.gov/36222184/

4. Guzzi, Nicola, Cieśla, Maciej, Ngoc, Phuong Cao Thi, Hsieh, Andrew C, Bellodi, Cristian. 2018. Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells. In Cell, 173, 1204-1216.e26. doi:10.1016/j.cell.2018.03.008. https://pubmed.ncbi.nlm.nih.gov/29628141/

5. Martinez, Nicole M, Su, Amanda, Burns, Margaret C, Yeo, Gene W, Gilbert, Wendy V. 2022. Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing. In Molecular cell, 82, 645-659.e9. doi:10.1016/j.molcel.2021.12.023. https://pubmed.ncbi.nlm.nih.gov/35051350/