Not4-dependent targeting of MMF1 mRNA to mitochondria limits its expression via ribosome pausing, Egd1 ubiquitination, Caf130, no-go-decay and autophagy.

Autor:	Chen S; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Institute of Genetics and Genomics of Geneva, Geneva, Switzerland., Allen G; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Institute of Genetics and Genomics of Geneva, Geneva, Switzerland., Panasenko OO; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Institute of Genetics and Genomics of Geneva, Geneva, Switzerland., Collart MA; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Institute of Genetics and Genomics of Geneva, Geneva, Switzerland.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2023 Jun 09; Vol. 51 (10), pp. 5022-5039.
DOI:	10.1093/nar/gkad299
Abstrakt:	The Ccr4-Not complex is a conserved multi protein complex with diverse roles in the mRNA life cycle. Recently we determined that the Not1 and Not4 subunits of Ccr4-Not inversely regulate mRNA solubility and thereby impact dynamics of co-translation events. One mRNA whose solubility is limited by Not4 is MMF1 encoding a mitochondrial matrix protein. In this work we uncover a mechanism that limits MMF1 overexpression and depends upon its co-translational targeting to the mitochondria. We have named this mechanism Mito-ENCay. This mechanism relies on Not4 promoting ribosome pausing during MMF1 translation, and hence the co-translational docking of the MMF1 mRNA to mitochondria via the mitochondrial targeting sequence of the Mmf1 nascent chain, the Egd1 chaperone, the Om14 mitochondrial outer membrane protein and the co-translational import machinery. Besides co-translational Mitochondrial targeting, Mito-ENCay depends upon Egd1 ubiquitination by Not4, the Caf130 subunit of the Ccr4-Not complex, the mitochondrial outer membrane protein Cis1, autophagy and no-go-decay. (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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