多形体
翻译(生物学)
基因敲除
生物
信使核糖核酸
细胞质
P-体
细胞生物学
下调和上调
聚腺苷酸
分子生物学
核糖核酸
生物化学
基因
核糖体
作者
Ting Shan,Feiyan Liu,Miaomiao Wen,Zonggui Chen,Shaopeng Li,Yafen Wang,Hong Cheng,Yu Zhou
出处
期刊:Molecular Cell
[Elsevier]
日期:2023-11-27
卷期号:83 (24): 4494-4508.e6
被引量:8
标识
DOI:10.1016/j.molcel.2023.10.040
摘要
In the cytoplasm, mRNAs are dynamically partitioned into translating and non-translating pools, but the mechanism for this regulation has largely remained elusive. Here, we report that m6A regulates mRNA partitioning between polysome and P-body where a pool of non-translating mRNAs resides. By quantifying the m6A level of polysomal and cytoplasmic mRNAs with m6A-LAIC-seq and m6A-LC-MS/MS in HeLa cells, we observed that polysome-associated mRNAs are hypo-m6A-methylated, whereas those enriched in P-body are hyper-m6A-methylated. Downregulation of the m6A writer METTL14 enhances translation by switching originally hyper-m6A-modified mRNAs from P-body to polysome. Conversely, by proteomic analysis, we identify a specific m6A reader IGF2BP3 enriched in P-body, and via knockdown and molecular tethering assays, we demonstrate that IGF2BP3 is both necessary and sufficient to switch target mRNAs from polysome to P-body. These findings suggest a model for the dynamic regulation of mRNA partitioning between the translating and non-translating pools in an m6A-dependent manner.
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