eIF2
生物
综合应力响应
真核翻译
细胞生物学
起始因子
起始密码子
翻译(生物学)
内部核糖体进入位点
蛋白质生物合成
真核起始因子
EIF4A1
真核生物γ翻译起始因子4
遗传学
信使核糖核酸
基因
作者
Xin Shu,Yuanhui Mao,Longfei Jia,Shu‐Bing Qian
标识
DOI:10.1038/s41589-021-00913-4
摘要
In eukaryotic cells, many messenger RNAs (mRNAs) possess upstream open reading frames (uORFs) in addition to the main coding region. After uORF translation, the ribosome could either recycle at the stop codon or resume scanning for downstream start codons in a process known as reinitiation. Accumulating evidence suggests that some initiation factors, including eukaryotic initiation factor 3 (eIF3), linger on the early elongating ribosome, forming an eIF3-80S complex. Very little is known about how eIF3 is carried along with the 80S during elongation and whether the eIF3-80S association is subject to regulation. Here, we report that eIF3a undergoes dynamic O-linked N-acetylglucosamine (O-GlcNAc) modification in response to nutrient starvation. Stress-induced de-O-GlcNAcylation promotes eIF3 retention on the elongating ribosome and facilitates activating transcription factor 4 (ATF4) reinitiation. Eliminating the modification site from eIF3a via CRISPR genome editing induces ATF4 reinitiation even under the nutrient-rich condition. Our findings illustrate a mechanism in balancing ribosome recycling and reinitiation, thereby linking the nutrient stress response and translational reprogramming.
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