Dieter A. Wolf | Molecular Cell: eIF3 Associates with 80S Ribosomes to Promote Translation Elongation, Mitochondrial Homeostasis, and Muscle Health

Highlights

• eIF3—via eIF3e—promotes mRNA selective early translation elongation

• eIF3e-dependent mRNAs encode membrane, secretory, and organelle targeted proteins

• eIF3 travels with 80S ribosomes until nascent chains emerge for subcellular targeting

• In vivo, eIF3e promotes mitochondrial function and skeletal muscle health

Summary

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 ∼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.

Link: https://www.sciencedirect.com/science/article/pii/S1097276520303889