Mice with NOP2/sun RNA methyltransferase 5 deficiency die before reaching puberty due to fatal kidney damage.

Abstract

BACKGROUND: NOP2/Sun RNA methyltransferase 5 (NSUN5) is an RNA methyltransferase that has a broad distribution and plays critical roles in various biological processes. However, our knowledge of the biological functions of NSUN5 in mammals is very limited. Therefore, in this study, we investigate the role of NSUN5 in mice. METHODS: In the present research, we built a mouse model) using the CRISPR/Cas9 system to investigated the specific role of NSUN5. RESULTS: We observed thatmice had a reduced body weight compared to wild-type mice. Additionally, their survival rate gradually decreased to 20% after postnatal day (PD) 21. Further examination revealed themice had multiple organ damage, with the most severe damage occurring in the kidneys. Moreover, we observed glycogen deposition and fibrosis, along with a notable shorting of the primary foot processes of glomeruli inkidneys. Furthermore, we found that the kidneys ofmice showed increased expression of the apoptotic signal Caspase-3 and accumulated stronger DNA damage at PD 21. CONCLUSIONS: In our study, we found that mice lacking NSUN5 died before puberty due to kidney fatal damage caused by DNA damage and cell apoptosis. These results suggest that NSUN5 plays a vital role in preventing the accumulation of DNA damage and cell apoptosis in the kidney.