Not1 and Not4 inversely determine mRNA solubility that sets the dynamics of co-translational events

Allen, George and Weiss, Benjamin and Panasenko, Olesya O. and Huch, Susanne and Villanyi, Zoltan and Albert, Benjamin and Dilg, Daniel and Zagatti, Marina and Schaughency, Paul and Liao, Susan E. and Corden, Jeff and Polte, Christine and Shore, David and Ignatova, Zoya and Pelechano, Vicent and Collart, Martine A. (2023) Not1 and Not4 inversely determine mRNA solubility that sets the dynamics of co-translational events. GENOME BIOLOGY, 24 (1). ISSN 1474-7596

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Background: The Ccr4-Not complex is mostly known as the major eukaryotic dead- enylase. However, several studies have uncovered roles of the complex, in particular of the Not subunits, unrelated to deadenylation and relevant for translation. In particu- lar, the existence of Not condensates that regulate translation elongation dynamics has been reported. Typical studies that evaluate translation efficiency rely on soluble extracts obtained after the disruption of cells and ribosome profiling. Yet cellular mRNAs in condensates can be actively translated and may not be present in such extracts. Results: In this work, by analyzing soluble and insoluble mRNA decay intermediates in yeast, we determine that insoluble mRNAs are enriched for ribosomes dwelling at non- optimal codons compared to soluble mRNAs. mRNA decay is higher for soluble RNAs, but the proportion of co-translational degradation relative to the overall mRNA decay is higher for insoluble mRNAs. We show that depletion of Not1 and Not4 inversely impacts mRNA solubilities and, for soluble mRNAs, ribosome dwelling according to codon optimality. Depletion of Not4 solubilizes mRNAs with lower non-optimal codon content and higher expression that are rendered insoluble by Not1 depletion. By con- trast, depletion of Not1 solubilizes mitochondrial mRNAs, which are rendered insoluble upon Not4 depletion. Conclusions: Our results reveal that mRNA solubility defines the dynamics of co- translation events and is oppositely regulated by Not1 and Not4, a mechanism that we additionally determine may already be set by Not1 promoter association in the nucleus.

Item Type: Article
Subjects: Q Science / természettudomány > QD Chemistry / kémia
Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
Depositing User: MTMT SWORD
Date Deposited: 22 Feb 2024 14:47
Last Modified: 22 Feb 2024 14:47

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