关键词: 关键词：RNA m6A甲基化, YTHDC1, 小脑发育, 髓母细胞瘤

Abstract: Objective To study the expression pattern of RNA m6A binding protein YTHDC1 during mouse cerebellar development and in human medulloblastoma. Methods Relative expression level of YTHDC1 RNA in the mice cerebellum, medulloblastoma and Daoy cell lines were analyzed based on RNA-seq results. Western blot and immunohistochemical staining were performed to detect the expression of YTHDC1 protein. The methyltransferase METTL3 was knocked down in Daoy cells, followed by m6A-IP-qPCR method to detect the change in YTHDC1 methylation level and the subsequent effect on the YTHDC1 protein level. Results During mice cerebellar development, the YTHDC1 expression remained constant in RNA level but showed a gradual reduction in protein level. Similarly, the expression of YTHDC1 protein in internal granular layer decreased significantly from postnatal day 7 (P7) to P60. Comparison between medulloblastoma tissues and adjacent para-carcinoma tissues, showed no apparent change of YTHDC1 in RNA level, but a significant decrease in protein level. Notably, YTHDC1 RNA methylation level increased in medulloblastoma, and the decreased m6A methylation level of YTHDC1 caused by METTL3 knockdown resulted in increased YTHDC1 protein expression. Conclusions In both cerebellar development and medulloblastoma, a dynamic change of YTHDC1 protein expression， but not YTHDC1 RNA, was observed. The RNA m6A modification of YTHDC1 can regulate its protein expression at post-transcriptional level, suggesting that RNA m6A methylation of YTHDC1 may impact on cerebellar development and medulloblastoma through regulating its protein expression.

Key words: Key words: RNA m6A methylation, YTHDC1, cerebellar development, medulloblastoma