生物
N6-甲基腺苷
甲基转移酶
核糖核酸
细胞生物学
信使核糖核酸
翻译(生物学)
基因敲除
遗传学
分子生物学
DNA
基因
甲基化
作者
Shanshan Xie,Wenjun Kuang,Mengzhe Guo,Feng Yang,Hao Jin,Xiying Chen,Li Yi,Chunxiao Huo,Zhangqi Xu,Aifu Lin,Wei Liu,Jianhua Mao,Qiang Shu,Tianhua Zhou
标识
DOI:10.1083/jcb.202307002
摘要
N6, 2′-O-dimethyladenosine (m6Am) is a widespread RNA modification catalyzed by the methyltransferase PCIF1 (phosphorylated CTD interacting factor 1). Despite its prevalence, the biological functions of m6Am in RNA remain largely elusive. Here, we report a critical role of PCIF1-dependent m6Am RNA modification in ciliogenesis in RPE-1 cells. Our findings demonstrate that PCIF1 acts as a negative regulator of ciliation through its m6Am methyltransferase activity. A quantitative proteomic analysis identifies BICD2 as a downstream target of PCIF1, with PCIF1 depletion resulting in a significant increase in BICD2 levels. BICD2 depletion leads to a significant reduction in ciliation. Crucially, the ciliary phenotype in PCIF1-depleted cells is reversed upon BICD2 knockdown. Further investigations reveal that PCIF1 regulates BICD2 protein levels through its m6Am catalytic activity, which reduces the stability and translation efficiency of BICD2 mRNA. Single-base resolution LC-MS analysis identifies the m6Am site on BICD2 mRNA modified by PCIF1. These findings establish the essential involvement of PCIF1-dependent m6Am modification in ciliogenesis.
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