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

Article Article scientifique Article Not4 and Not5 modulate translation elongation by Rps7A ubiquitination, Rli1 moonlighting, and condensates that exclude eIF5A eng 2021 author Allen George Edward 911276 author Panasenko Olesya 629191 author Villanyi Zoltan 766412 author Zagatti Marina 885449 author Weiss Benjamin 689060 author Pagliazzo Lucile 931799 author Huch Susanne author Polte Christine author Zahoran Szabolcs 913585 author Hughes Christopher S. author Pelechano Vicent author Ignatova Zoya author Collart Martine 0000-0001-6955-1773 27009 109633 10.1016/j.celrep.2021.109633 34469733 2211-1247 https://linkinghub.elsevier.com/retrieve/pii/S2211124721010767 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. Not1 Not4 Not5 Condensates Translation elongation EIF5A Rli1 Codon optimality Dewey 616 Dewey 590 Swiss National Science Foundation Genetic and biochemical analysis of the regulation of gene expression by the Ccr4-Not complex in the yeast S.cerevisiae 31003A_172999 CH Project funding 23 Institut de génétique et de génomique 0DH 54 Département de microbiologie et médecine moléculaire 21B false 58 Caractérisation génétique et biochimique du complexe Ccr4-Not conservé. 81 https://doi.org/10.5281/zenodo.5150443 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137567 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137613 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE168290 Cell Reports 36 9 92705e1e-c080-402d-86fe-fcf4d0a56f75 Article (Published version) Public 1-s2.0-S2211124721010767-main.pdf 3213904 application/pdf CC BY 986ce512-7029-4adf-8b55-90c3ba496e11 Supplemental data Public ScienceDirect_files_02Sep2021_09-22-57.766.zip 53495160 application/zip Vignette Public 1-s2.0-S2211124721010767-fx1.jpg 33942 image/jpeg openAccess Centres et instituts / Institut de génétique et de génomique Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

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Not4 and Not5 modulate translation elongation by Rps7A ubiquitination, Rli1 moonlighting, and condensates that exclude eIF5A	Cell Reports			2021	495	290

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Pagliazzo, Lucile