Reference: Chen S, et al. (2023) Not4-dependent targeting of MMF1 mRNA to mitochondria limits its expression via ribosome pausing, Egd1 ubiquitination, Caf130, no-go-decay and autophagy. Nucleic Acids Res 51(10):5022-5039

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Abstract


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.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Chen S, Allen G, Panasenko OO, Collart MA
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