Rnh1-KO Mouse

Rnh1, also known as ribonuclease inhibitor 1 or angiogenin inhibitor 1, is a ubiquitously expressed leucine-rich repeat protein highly conserved in mammalian species. It is an accessory part of the translation machinery. Rnh1 binds to angiogenin (ANG) to inhibit its ribonucleolytic activity and can also bind to 40S ribosomes, potentially controlling translation. It is involved in processes like cell homeostasis, and its dysregulation is associated with various diseases [1].

In mice, inactivation of rnh1 causes embryonically lethal anemia [4]. In humans, a homozygous splice-site variant in RNH1 leads to a multiorgan developmental disease with congenital cataract, global developmental delay, myopathy, psychomotor deterioration, seizures, and periodic anemia associated with upper respiratory tract infections [4]. Biallelic variants in RNH1 confer susceptibility to a subtype of acute, necrotizing encephalopathy in previously healthy children [5]. In bladder cancer, low RNH1 expression is associated with enhanced invasion and metastasis, and it can predict immunotherapy response [2]. In lung adenocarcinoma, E2F1 binds to the RNH1 promoter to inhibit its expression, promoting cancer development [3].

In conclusion, Rnh1 plays essential roles in multiple biological processes. Its inactivation in mouse models reveals its importance in preventing anemia. In human studies, genetic variants of RNH1 are linked to diseases such as multiorgan developmental disorders and acute necrotizing encephalopathy. In cancer, RNH1 is involved in regulating cancer cell invasion, metastasis, and response to immunotherapy, highlighting its significance in disease-related research.

References:

1. Sarangdhar, Mayuresh Anant, Allam, Ramanjaneyulu. 2021. Angiogenin (ANG)-Ribonuclease Inhibitor (RNH1) System in Protein Synthesis and Disease. In International journal of molecular sciences, 22, . doi:10.3390/ijms22031287. https://pubmed.ncbi.nlm.nih.gov/33525475/

2. Chen, Sen, Ran, Jun, Fan, Zhouqian, Peng, Jian, Hu, Zuquan. 2023. Functional status analysis of RNH1 in bladder cancer for predicting immunotherapy response. In Scientific reports, 13, 12625. doi:10.1038/s41598-023-39827-7. https://pubmed.ncbi.nlm.nih.gov/37537337/

3. Zhao, Wenyue, Liu, Yang, Yang, Ying, Wang, Liming. 2024. New link between RNH1 and E2F1: regulates the development of lung adenocarcinoma. In BMC cancer, 24, 635. doi:10.1186/s12885-024-12392-6. https://pubmed.ncbi.nlm.nih.gov/38783241/

4. Hedberg-Oldfors, Carola, Mitra, Sanhita, Molinaro, Angela, Sterky, Fredrik H, Darin, Niklas. 2023. Ribonuclease inhibitor 1 (RNH1) deficiency cause congenital cataracts and global developmental delay with infection-induced psychomotor regression and anemia. In European journal of human genetics : EJHG, 31, 887-894. doi:10.1038/s41431-023-01327-7. https://pubmed.ncbi.nlm.nih.gov/36935417/

5. Shashi, Vandana, Schoch, Kelly, Ganetzky, Rebecca, Innes, A Micheil, Davis, Erica E. 2023. Biallelic variants in ribonuclease inhibitor (RNH1), an inflammasome modulator, are associated with a distinctive subtype of acute, necrotizing encephalopathy. In Genetics in medicine : official journal of the American College of Medical Genetics, 25, 100897. doi:10.1016/j.gim.2023.100897. https://pubmed.ncbi.nlm.nih.gov/37191094/