Translation factor and RNA binding protein mRNA interactomes support broader RNA regulons for posttranscriptional control

Kershaw, Christopher J.; Nelson, Michael G.; Castelli, Lydia M.; Jennings, Martin D.; Lui, Jennifer; Talavera, David; Grant, Chris M.; Pavitt, Graham D.; Hubbard, Simon J.; Ashe, Mark P.

doi:10.1016/j.jbc.2023.105195

Cited by 5 publications

References 102 publications

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Orchestrated centers for the production of proteins or “translation factories”

Crawford,

Eastham,

Pool

et al. 2024

WIREs RNA

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The mechanics of how proteins are generated from mRNA is increasingly well understood. However, much less is known about how protein production is coordinated and orchestrated within the crowded intracellular environment, especially in eukaryotic cells. Recent studies suggest that localized sites exist for the coordinated production of specific proteins. These sites have been termed “translation factories” and roles in protein complex formation, protein localization, inheritance, and translation regulation have been postulated. In this article, we review the evidence supporting the translation of mRNA at these sites, the details of their mechanism of formation, and their likely functional significance. Finally, we consider the key uncertainties regarding these elusive structures in cells.This article is categorized under: Translation Translation > Mechanisms RNA Export and Localization > RNA Localization Translation > Regulation

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Orchestrated centers for the production of proteins or “translation factories”

Crawford,

Eastham,

Pool

et al. 2024

WIREs RNA

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Investigating the role of RNA-binding protein Ssd1 in aneuploidy tolerance through network analysis

Dutcher,

Gasch

2024

Preprint

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RNA-binding proteins (RBPs) play critical cellular roles by mediating various stages of RNA life cycles. Ssd1, an RBP with pleiotropic effects, has been implicated in aneuploidy tolerance inSaccharomyces cerevisiaebut its mechanistic role remains unclear. Here we used a network-based approach to inform on Ssd1’s role in aneuploidy tolerance, by identifying and experimentally perturbing a network of RBPs that share mRNA targets with Ssd1. We identified RBPs whose bound mRNA targets significantly overlap with Ssd1 targets. For 14 identified RBPs, we then used a genetic approach to generate all combinations of genotypes for euploid and aneuploid yeast with an extra copy of chromosome XII, with and withoutSSD1and/or the RBP of interest. Deletion of 10 RBPs either exacerbated or alleviated the sensitivity of wild-type and/orssd1Δ cells to chromosome XII duplication, in several cases indicating genetic interactions withSSD1in the context of aneuploidy. We integrated these findings with results from a global over-expression screen that identified genes whose duplication complementsssd1Δ aneuploid sensitivity. The resulting network points to a sub-group of proteins with shared roles in translational repression and p-body formation, implicating these functions in aneuploidy tolerance. Our results reveal a role for new RBPs in aneuploidy tolerance and support a model in which Ssd1 mitigates translation-related stresses in aneuploid cells.

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Translation efficiency covariation across cell types is a conserved organizing principle of mammalian transcriptomes

Liu,

Hoskins,

Geng

et al. 2024

Preprint

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Characterization of shared patterns of RNA expression between genes across conditions has led to the discovery of regulatory networks and novel biological functions. However, it is unclear if such coordination extends to translation, a critical step in gene expression. Here, we uniformly analyzed 3,819 ribosome profiling datasets from 117 human and 94 mouse tissues and cell lines. We introduce the concept ofTranslation Efficiency Covariation(TEC), identifying coordinated translation patterns across cell types. We nominate potential mechanisms driving shared patterns of translation regulation. TEC is conserved across human and mouse cells and helps uncover gene functions. Moreover, our observations indicate that proteins that physically interact are highly enriched for positive covariation at both translational and transcriptional levels. Our findings establish translational covariation as a conserved organizing principle of mammalian transcriptomes.

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Translation factor and RNA binding protein mRNA interactomes support broader RNA regulons for posttranscriptional control

Cited by 5 publications

References 102 publications

Orchestrated centers for the production of proteins or “translation factories”

Orchestrated centers for the production of proteins or “translation factories”

Investigating the role of RNA-binding protein Ssd1 in aneuploidy tolerance through network analysis

Translation efficiency covariation across cell types is a conserved organizing principle of mammalian transcriptomes

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