Rnmt-KO Mouse

Rnmt, short for RNA guanine-7 methyltransferase, is a crucial enzyme in eukaryotic gene expression. It catalyzes the N7 methylation of the cap guanosine in the mRNA cap formation process, which is essential for mRNA processing, translation initiation, and nuclear RNA export [4,5,6]. This process is involved in various biological pathways such as cell differentiation, proliferation, and ribosome biogenesis [1,2].

In T cell activation, Rnmt is induced by TCR stimulation and coordinates the production of mRNA, snoRNA, and rRNA required for ribosome biogenesis. Rnmt cKO CD4 T cells show decreased ribosome synthesis, reduced translation rates, and proliferation failure, indicating its essential role in T cell activation [2]. In osteosarcoma, Rnmt collaborates with CYFIP1 to induce the m7G methylation of AURKAIP1 mRNA, leading to cuproptosis in OS cells, thus suppressing OS occurrence and progression [3]. In breast cancer cells, oncogenic PIK3CA mutations increase the dependency on Rnmt for proliferation. When Rnmt activity is reduced, a subset of breast cancer cells with PIK3CA mutations exhibit reduced proliferation and increased apoptosis [7].

In conclusion, Rnmt is vital for mRNA cap methylation, which has far-reaching impacts on gene expression and various biological processes. Through gene knockout (KO) or conditional knockout (CKO) mouse models, its role in diseases like T cell-related disorders, osteosarcoma, and breast cancer has been revealed, providing potential therapeutic targets for these diseases.

References:

1. Liang, Shang, Almohammed, Rajaei, Cowling, Victoria H. . The RNA cap methyltransferases RNMT and CMTR1 co-ordinate gene expression during neural differentiation. In Biochemical Society transactions, 51, 1131-1141. doi:10.1042/BST20221154. https://pubmed.ncbi.nlm.nih.gov/37145036/

2. Galloway, Alison, Kaskar, Aneesa, Ditsova, Dimitrinka, Jemielity, Jacek, Cowling, Victoria H. . Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation. In Nucleic acids research, 49, 6722-6738. doi:10.1093/nar/gkab465. https://pubmed.ncbi.nlm.nih.gov/34125914/

3. Lin, Zili, Wu, Ziyi, He, Yizhe, Li, Xiangyao, Luo, Wei. 2025. CYFIP1 coordinate with RNMT to induce osteosarcoma cuproptosis via AURKAIP1 m7G modification. In Molecular medicine (Cambridge, Mass.), 31, 74. doi:10.1186/s10020-025-01127-3. https://pubmed.ncbi.nlm.nih.gov/39984834/

4. Aregger, Michael, Kaskar, Aneesa, Varshney, Dhaval, Weidlich, Simone, Cowling, Victoria H. . CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription. In Molecular cell, 61, 734-746. doi:10.1016/j.molcel.2016.02.008. https://pubmed.ncbi.nlm.nih.gov/26942677/

5. Osborne, Michael J, Volpon, Laurent, Memarpoor-Yazdi, Mina, Cowling, Victoria H, Borden, Katherine L B. 2022. Identification and Characterization of the Interaction Between the Methyl-7-Guanosine Cap Maturation Enzyme RNMT and the Cap-Binding Protein eIF4E. In Journal of molecular biology, 434, 167451. doi:10.1016/j.jmb.2022.167451. https://pubmed.ncbi.nlm.nih.gov/35026230/

6. Aregger, Michael, Cowling, Victoria H. . Human cap methyltransferase (RNMT) N-terminal non-catalytic domain mediates recruitment to transcription initiation sites. In The Biochemical journal, 455, 67-73. doi:10.1042/BJ20130378. https://pubmed.ncbi.nlm.nih.gov/23863084/

7. Dunn, Sianadh, Lombardi, Olivia, Lukoszek, Radoslaw, Cowling, Victoria H. . Oncogenic PIK3CA mutations increase dependency on the mRNA cap methyltransferase, RNMT, in breast cancer cells. In Open biology, 9, 190052. doi:10.1098/rsob.190052. https://pubmed.ncbi.nlm.nih.gov/30991934/