生物
信使核糖核酸
RNA结合蛋白
翻译(生物学)
聚腺苷酸
无意义介导的衰变
P-体
细胞生物学
多形体
转录组
核糖核酸
基因表达
遗传学
基因
核糖体
RNA剪接
作者
Tatsuaki Kurosaki,Shuhei Mitsutomi,Alexander Hewko,Nobuyoshi Akimitsu,Lynne E. Maquat
出处
期刊:Molecular Cell
[Elsevier]
日期:2022-12-01
卷期号:82 (23): 4564-4581.e11
被引量:7
标识
DOI:10.1016/j.molcel.2022.10.018
摘要
How fragile X syndrome protein (FMRP) binds mRNAs and regulates mRNA metabolism remains unclear. Our previous work using human neuronal cells focused on mRNAs targeted for nonsense-mediated mRNA decay (NMD), which we showed are generally bound by FMRP and destabilized upon FMRP loss. Here, we identify >400 high-confidence FMRP-bound mRNAs, only ∼35% of which are NMD targets. Integrative transcriptomics together with SILAC-LC-MS/MS reveal that FMRP loss generally results in mRNA destabilization and more protein produced per FMRP target. We use our established RIP-seq technology to show that FMRP footprints are independent of protein-coding potential, target GC-rich and structured sequences, and are densest in 5' UTRs. Regardless of where within an mRNA FMRP binds, we find that FMRP protects mRNAs from deadenylation and directly binds the cytoplasmic poly(A)-binding protein. Our results reveal how FMRP sequesters polyadenylated mRNAs into stabilized and translationally repressed complexes, whose regulation is critical for neurogenesis and synaptic plasticity.
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