Increasing evidences suggest that the methyltransferase NSUN2 catalyzes 5-methylcytosine(m5C)modifications on viral RNAs,which are essential for the replication of various viruses.Despite the function of m5C depositio...Increasing evidences suggest that the methyltransferase NSUN2 catalyzes 5-methylcytosine(m5C)modifications on viral RNAs,which are essential for the replication of various viruses.Despite the function of m5C deposition is well characterized,other potential roles of NSUN2 in regulating viral replication remain largely unknown.In this study,the m5C modified residues catalyzed by NSUN2 on enterovirus 71(EV71)RNAs were mapped.NSUN2,along with m5C modifications,played multiple roles during the EV71 life cycle.Functional m5C modified nucleotides increased the translational efficiency and stability of EV71 RNAs.Additionally,NSUN2 was found to target the viral protein VP1 for binding and promote its stability by inhibiting the ubiquitination.Furthermore,both viral replication and pathogenicity in mice were largely attenuated when functional m5C residues were mutated.Taken together,this study characterizes distinct pathways mediated by NSUN2 in regulating EV71 replication,and highlights the importance of its catalyzed m5C modifications on EV71 RNAs for the viral replication and pathogenicity.展开更多
基金supported by the National Natural Science Foundation of China(31970168)the Key R&D Program of Hubei Province(2021BCD004)+2 种基金the Hubei Central Leading Local Science and Technology Special Project(2022BGE245)the Hubei Science and Technology Major Project[2021ACB004]the Wuhan Knowledge Innovation Special Project(2023020201020303).
文摘Increasing evidences suggest that the methyltransferase NSUN2 catalyzes 5-methylcytosine(m5C)modifications on viral RNAs,which are essential for the replication of various viruses.Despite the function of m5C deposition is well characterized,other potential roles of NSUN2 in regulating viral replication remain largely unknown.In this study,the m5C modified residues catalyzed by NSUN2 on enterovirus 71(EV71)RNAs were mapped.NSUN2,along with m5C modifications,played multiple roles during the EV71 life cycle.Functional m5C modified nucleotides increased the translational efficiency and stability of EV71 RNAs.Additionally,NSUN2 was found to target the viral protein VP1 for binding and promote its stability by inhibiting the ubiquitination.Furthermore,both viral replication and pathogenicity in mice were largely attenuated when functional m5C residues were mutated.Taken together,this study characterizes distinct pathways mediated by NSUN2 in regulating EV71 replication,and highlights the importance of its catalyzed m5C modifications on EV71 RNAs for the viral replication and pathogenicity.
