Rpia-KO Mouse

RPIA, ribose 5-phosphate isomerase A, is an enzyme-encoding gene. It is a key enzyme in the pentose phosphate pathway, catalyzing the interconversion of ribose-5-phosphate and ribulose-5-phosphate [4,5]. This pathway is crucial for producing NADPH and pentose precursors for nucleotides, thus playing an important role in cell metabolism, proliferation, and nucleotide biosynthesis [6]. Genetic models can be used to study its function and how it impacts biological processes and diseases.

RPIA deficiency is linked to a rare genetic leukoencephalopathy [1]. In Enterobacter cloacae, mutation of rpiA decreases seed and root colonization and biocontrol of damping-off, indicating its role in plant-microbe interactions [4]. In human endometrial cancer cells, knockdown of RPIA reduces cell proliferation, glycolytic capacity, and oxidative phosphorylation, suggesting its importance in cancer cell metabolism [2]. In human colorectal cancer cells, miR124 targets RPIA mRNA, reducing the pentose phosphate pathway and cell proliferation [3]. In macrophages, the antiviral effector PKR phosphorylates and inhibits RPIA, suppressing nucleic acid synthesis during the immune response to RNA [6].

In conclusion, RPIA is essential for the pentose phosphate pathway, influencing various biological processes. Its study through genetic models has revealed its significance in diseases such as rare genetic leukoencephalopathy and cancer, as well as in plant-microbe interactions and the immune response. Understanding RPIA's function provides insights into disease mechanisms and potential treatment strategies.

References:

1. Kaur, Parneet, Wamelink, Mirjam M C, van der Knaap, Marjo S, Girisha, Katta Mohan, Shukla, Anju. 2019. Confirmation of a Rare Genetic Leukoencephalopathy due to a Novel Bi-allelic Variant in RPIA. In European journal of medical genetics, 62, 103708. doi:10.1016/j.ejmg.2019.103708. https://pubmed.ncbi.nlm.nih.gov/31247379/

2. Szwarc, Maria M, Kommagani, Ramakrishna, Putluri, Vasanta, Lydon, John P, O'Malley, Bert W. 2018. Steroid Receptor Coactivator-2 Controls the Pentose Phosphate Pathway through RPIA in Human Endometrial Cancer Cells. In Scientific reports, 8, 13134. doi:10.1038/s41598-018-31372-y. https://pubmed.ncbi.nlm.nih.gov/30177747/

3. Qiu, Zhaoping, Guo, Weijie, Wang, Qifeng, Zhao, Yingjun, He, Xianghuo. 2015. MicroRNA-124 reduces the pentose phosphate pathway and proliferation by targeting PRPS1 and RPIA mRNAs in human colorectal cancer cells. In Gastroenterology, 149, 1587-1598.e11. doi:10.1053/j.gastro.2015.07.050. https://pubmed.ncbi.nlm.nih.gov/26248089/

4. Lohrke, Scott M, Dery, Pierre D, Li, Wei, Kobayashi, Donald Y, Roberts, Daniel R. . Mutation of rpiA in Enterobacter cloacae decreases seed and root colonization and biocontrol of damping-off caused by Pythium ultimum on cucumber. In Molecular plant-microbe interactions : MPMI, 15, 817-25. doi:. https://pubmed.ncbi.nlm.nih.gov/12182339/

5. Hove-Jensen, B, Maigaard, M. . Escherichia coli rpiA gene encoding ribose phosphate isomerase A. In Journal of bacteriology, 175, 5628-35. doi:. https://pubmed.ncbi.nlm.nih.gov/8366047/

6. Bhattacharjee, Pushpak, Wang, Die, Anderson, Dovile, Harris, Lawrence D, Sadler, Anthony J. 2024. The immune response to RNA suppresses nucleic acid synthesis by limiting ribose 5-phosphate. In The EMBO journal, 43, 2636-2660. doi:10.1038/s44318-024-00100-w. https://pubmed.ncbi.nlm.nih.gov/38778156/