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eIF3 Associates with 80S Ribosomes to Promote Translation Elongation, Mitochondrial Homeostasis, and Muscle Health.
- Source :
-
Molecular Cell . Aug2020, Vol. 79 Issue 4, p575-575. 1p. - Publication Year :
- 2020
-
Abstract
- 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. • 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 Lin et al. discovered that, in addition to its function in canonical translation initiation, multi-subunit eIF3 migrates with post-initiation 80S ribosomes to promote early translation elongation of mRNAs encoding organellar, secretory, and membrane-targeted proteins. Loss of eIF3's elongation and subcellular targeting activity leads to mitochondrial and skeletal muscle dysfunction. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10972765
- Volume :
- 79
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Molecular Cell
- Publication Type :
- Academic Journal
- Accession number :
- 145207559
- Full Text :
- https://doi.org/10.1016/j.molcel.2020.06.003