Not4 and Not5 modulate translation elongation by Rps7A ubiquitination, Rli1 moonlighting, and condensates that exclude eIF5A.

Autor:	Allen GE; Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland., Panasenko OO; Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland., Villanyi Z; Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, 6726 Szeged, Hungary., Zagatti M; Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland., Weiss B; Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland., Pagliazzo L; Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland., Huch S; SciLifeLab, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17165 Solna, Sweden., Polte C; Institute of Biochemistry and Molecular Biology, University of Hamburg, 20146 Hamburg, Germany., Zahoran S; Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, 6726 Szeged, Hungary., Hughes CS; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z1L3, Canada., Pelechano V; SciLifeLab, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17165 Solna, Sweden., Ignatova Z; Institute of Biochemistry and Molecular Biology, University of Hamburg, 20146 Hamburg, Germany., Collart MA; Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland. Electronic address: martine.collart@unige.ch.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Aug 31; Vol. 36 (9), pp. 109633.
DOI:	10.1016/j.celrep.2021.109633
Abstrakt:	In this work, we show that Not4 and Not5 from the Ccr4-Not complex modulate translation elongation dynamics and change ribosome A-site dwelling occupancy in a codon-dependent fashion. These codon-specific changes in not5Δ cells are very robust and independent of codon position within the mRNA, the overall mRNA codon composition, or changes of mRNA expression levels. They inversely correlate with codon-specific changes in cells depleted for eIF5A and positively correlate with those in cells depleted for ribosome-recycling factor Rli1. Not5 resides in punctate loci, co-purifies with ribosomes and Rli1, but not with eIF5A, and limits mRNA solubility. Overexpression of wild-type or non-complementing Rli1 and loss of Rps7A ubiquitination enable Not4 E3 ligase-dependent translation of polyarginine stretches. We propose that Not4 and Not5 modulate translation elongation dynamics to produce a soluble proteome by Rps7A ubiquitination, dynamic condensates that limit mRNA solubility and exclude eIF5A, and a moonlighting function of Rli1. Competing Interests: Declaration of interests There are no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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