【摘 要】
：
The impact of methylation of the 3-untranslated region of an mRNA remains largely unknown.Here,we report that NSun2,a tRNAmethyltransferase,potently inhibit
【机 构】
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北京大学医学部生物化学与分子生物学系
【出 处】
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2014年衰老与转化医学研讨会暨第三届全国老年健康与转化医学论坛
论文部分内容阅读
The impact of methylation of the 3-untranslated region of an mRNA remains largely unknown.Here,we report that NSun2,a tRNAmethyltransferase,potently inhibits the turnover of p16INK4 mRNA.Knockdown of NSun2 reduced p16 expression by shortening the half-life of the p16 mRNA,while overexpression of NSun2 stabilized the p16 mRNA.In vitro methylation assays showed that NSun2 methylates the p16 3UTR at A988.Knockdown of NSun2 reduced the stability of the EGFP-p16 chimeric reporter transcripts bearing wild-type p16 3UTR,but not p16 3UTR with a mutated methylation site.Methylation by NSun2 prevented the association of p16 3UTR with HuR,AUF1,and Ago2/RISC,and prevented the recruitment of EGFP-p16 3UTR chimeric transcripts to processing bodies.In response to oxidative stress,NSun2 was essential for elevating p16 expression levels.In sum,NSun2-mediated methylation of the p16 3UTR is a novel mechanism to stabilize p16 mRNA.
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