The RING2/RNF2 E3-ubiquitin Ligases Effect The Oligodendrocytes Development And The Preliminary Mechanism Discussion

In the central nervous system,oligodendrocytes form myelin structures,wrap axons to protect axons and to increase the speed of impulse propagation along nerve fibers.Abnormal development of myelin sheath results in demyelinating diseases.RNF2(Ring1B/Ring2)is an E3 ubiquitin ligase and also as a core catalytic subunit in the Polycomb repressive complex 1,regulates the transcription of its target genes through chromatin modification.At present,a large number of studies have reported that RNF2 is involved in the development of neural stem cells,but its role in the development of oligodendrocytes is rarely reported.Using rat primary oligodendrocytes,we investigate the role of RNF2 in its development in this study.Oligodendrocytes express RNF2 dynamically.And we showed that RNF2 could affect the proliferation,differentiation and apoptosis in oligodendrocytes.The results of BrdU and Ki67 staining showed that the expression pattern of RNF2 was associated with the proliferation rate of oligodendrocytes.Overexpression of RNF2 inhibited oligodendrocytes differentiation,whereas knocking-down of RNFs induced differerentiation,as indicated by the expression of myelin basic protein(MBP).RNF 2 could also affect the apoptosis of oligodendrocytes.Using the RNA-seq analysis,we found that the myelin-associated proteins,cell development-related genes,and genes in NF-κB signaling were changed by RNF2 overexpression.We then confirmed that NF-κB signaling pathway was activated by RNFs.In addition,RNF2 also caused changes in ubiquitination of H2AK119 in oligodendrocytes.In summary,RNF2 may not only affect the development of oligodendrocytes through the NF-κB signaling pathway,but also affect the growth and differentiation of oligodendrocytes through the epigenetics modification.Our study demonstrated that the RNF2 gene indeed plays an important role in the development of oligodendrocytes and myelination.We hope that this study can provide new ideas and valuable references for studying the development of oligodendrocytes and the treatment of some diseases caused by demyelination.