PT  - JOURNAL ARTICLE
AU  - Yingying Lin
AU  - Fajin Li
AU  - Linlu Huang
AU  - Haoran Duan
AU  - Jianhuo Fang
AU  - Li Sun
AU  - Xudong Xing
AU  - Guiyou Tian
AU  - Yabin Cheng
AU  - Xuerui Yang
AU  - Dieter A. Wolf
TI  - eIF3 associates with 80S ribosomes to promote translation elongation, mitochondrial homeostasis, and muscle health
AID  - 10.1101/651240
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 651240
4099  - http://biorxiv.org/content/early/2019/12/22/651240.short
4100  - http://biorxiv.org/content/early/2019/12/22/651240.full
AB  - eIF3 is a multi-subunit complex with numerous functions in canonical translation initiation. eIF3 was also found 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 ∼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 ∼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.