elF3 Associates with 80S Ribosomes to Promote Translation Elongation, Mitochondria! Homeostasis, and Muscle Health
elF3 Associates with 80S Ribosomes to Promote Translation Elongation, Mitochondria! Homeostasis, and Muscle Health
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eIF3 与 80S 核糖体结合促进翻译伸长、线粒体稳态和肌肉健康
DOI：
10.1016/j.molcel.2020.06.003
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发表时间：
2020-08-20
期刊：
影响因子：
16
通讯作者：
Wolf, Dieter A.
中科院分区：
文献类型：
--
作者：
Lin, Yingying;Li, Fajin;Wolf, Dieter A.
eIF 3是一种多亚基复合物，在经典翻译起始中具有多种功能，已知与40 S和60 S核糖体蛋白和翻译延伸因子相互作用，但从未证明直接参与翻译延伸。我们发现eIF 3缺陷降低了一组类似于2，700种编码与线粒体和膜功能相关的蛋白质的mRNA的密码子25和75之间的早期核糖体延伸速度，导致其编码蛋白质的合成缺陷。为了促进延伸，eIF 3与翻译第一个类似于60个密码子的80 S核糖体相互作用，并用于招募蛋白质质量控制因子，这是正常线粒体生理学所需的功能。因此，eIF 3e（+/-）小鼠在骨骼肌中积累有缺陷的线粒体，并显示肌肉力量的进行性下降。因此，eIF 3与80 S核糖体相互作用，以在早期延伸水平上增强具有膜相关功能的蛋白质的合成，这是一种对线粒体生理学和肌肉健康至关重要的活性。
eIF3, a multi-subunit complex with numerous functions in canonical translation initiation, is known to interact with 40S and 60S ribosomal proteins and translation elongation factors, but a direct involvement in translation elongation has never been demonstrated. We found that eIF3 deficiency reduced early ribosomal elongation speed between codons 25 and 75 on a set of similar to 2,700 mRNAs encoding proteins associated with mitochondrial and membrane functions, resulting in defective synthesis of their encoded proteins. To promote elongation, eIF3 interacts with 80S ribosomes translating the first similar to 60 codons and serves to recruit protein quality-control factors, functions required for normal mitochondrial physiology. Accordingly, eIF3e(+/-) mice accumulate defective mitochondria in skeletal muscle and show a progressive decline in muscle strength. Hence, eIF3 interacts with 80S ribosomes to enhance, at the level of early elongation, the synthesis of proteins with membrane-associated functions, an activity that is critical for mitochondrial physiology and muscle health.