Yeast: Translation Regulation and Localized Translation

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 15244

Special Issue Editors

Faculty of Biology, Technion-Israel Institute if Technology, Haifa 32000, Israel
Interests: translation regulation; mRNA localization; RNA binding proteins; localized translation
Faculty of Biology, Technion - Israel Institute of Technology, Technion City, Haifa 3200003, Israel
Interests: translation; ribosome binding factors; protein biogenesis; protein folding; mRNA localization (co-translational protein folding, assembly and quality control pathways, in health and disease)

Special Issue Information

Dear Colleagues,

Translation regulation and localized translation are key for proper protein synthesis and hence essential for life. The protein products of these processes control the organism development, physiology, and behavior. Not surprisingly, mutations in these processes are implicated in cellular malfunctioning and diseases.

For many years, studies in yeast have provided crucial insights into these processes. Biochemical and molecular tools that are well-established in yeast have allowed a detailed understanding of protein factors and RNA elements that underlay these processes. Furthermore, recent high-throughput technologies have allowed system-wide modeling of regulation, under diverse growth conditions or cellular perturbations. Importantly, many of the concepts that were established in yeast appear relevant to many other organisms.

In this Special Issue, we wish to provide a stage to studies that encompass diverse aspects of translation regulation and localized translation in yeast. Of interest are, on the one hand, studies on molecular mechanisms that underlie translation regulation and localized translation, in particular resolving roles of RNA binding proteins and their target RNA sequences. On the other hand, studies at the global level, utilizing transcriptomics, proteomics or other high-throughput approaches, are highly encouraged.

The works presented here will provide a foundation for future developments in the field, either on aspects that are related to yeast physiology or on pathways that are conserved in other organisms.

Dr. Yoav Arava
Dr. Ayala Shiber
Guest Editors

Manuscript Submission Information

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Keywords

  • translation regulation
  • RNA localization
  • localized translation
  • RNA binding proteins
  • post-transcriptional regulation

Published Papers (6 papers)

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Editorial

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2 pages, 160 KiB  
Editorial
Yeast: Translation Regulation and Localized Translation
by Ayala Shiber and Yoav S. Arava
Microorganisms 2023, 11(3), 739; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms11030739 - 13 Mar 2023
Viewed by 967
Abstract
Translation regulation and localized translation are essential for protein synthesis, controlling all aspects of cellular function in health and disease [...] Full article
(This article belongs to the Special Issue Yeast: Translation Regulation and Localized Translation)

Research

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16 pages, 2410 KiB  
Article
Parameterising Translational Feedback Models of Autoregulatory RNA-Binding Proteins in Saccharomyces cerevisiae
by Michael Clarke-Whittet, Andrea Rocco and André P. Gerber
Microorganisms 2022, 10(2), 340; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10020340 - 01 Feb 2022
Cited by 2 | Viewed by 1931
Abstract
Post-transcriptional gene regulation is driven by RNA-binding proteins (RBPs). Recent global approaches suggest widespread autoregulation of RBPs through binding to their own mRNA; however, little is known about the regulatory impact and quantitative models remain elusive. By integration of several independent kinetic parameters [...] Read more.
Post-transcriptional gene regulation is driven by RNA-binding proteins (RBPs). Recent global approaches suggest widespread autoregulation of RBPs through binding to their own mRNA; however, little is known about the regulatory impact and quantitative models remain elusive. By integration of several independent kinetic parameters and abundance data, we modelled autoregulatory feedback loops for six canonical and non-canonical RBPs from the yeast Saccharomyces cerevisiae, namely Hrb1p, Hek2/Khd1p, Ski2p, Npl3p, Pfk2p, and Map1p. By numerically solving ordinary differential equations, we compared non-feedback models with models that considered the RPBs as post-transcriptional activators/repressors of their own expression. While our results highlight a substantial gap between predicted protein output and experimentally determined protein abundances applying a no-feedback model, addition of positive feedback loops are surprisingly versatile and can improve predictions towards experimentally determined protein levels, whereas negative feedbacks are particularly sensitive to cooperativity. Our data suggests that introduction of feedback loops supported by real data can improve models of post-transcriptional gene expression. Full article
(This article belongs to the Special Issue Yeast: Translation Regulation and Localized Translation)
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21 pages, 1675 KiB  
Article
Down-Regulation of Yeast Helicase Ded1 by Glucose Starvation or Heat-Shock Differentially Impairs Translation of Ded1-Dependent mRNAs
by Neelam Dabas Sen, Hongen Zhang and Alan G. Hinnebusch
Microorganisms 2021, 9(12), 2413; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9122413 - 23 Nov 2021
Cited by 6 | Viewed by 1747
Abstract
Ded1 is an essential DEAD-box helicase in yeast that broadly stimulates translation initiation and is critical for mRNAs with structured 5′UTRs. Recent evidence suggests that the condensation of Ded1 in mRNA granules down-regulates Ded1 function during heat-shock and glucose starvation. We examined this [...] Read more.
Ded1 is an essential DEAD-box helicase in yeast that broadly stimulates translation initiation and is critical for mRNAs with structured 5′UTRs. Recent evidence suggests that the condensation of Ded1 in mRNA granules down-regulates Ded1 function during heat-shock and glucose starvation. We examined this hypothesis by determining the overlap between mRNAs whose relative translational efficiencies (TEs), as determined by ribosomal profiling, were diminished in either stressed WT cells or in ded1 mutants examined in non-stress conditions. Only subsets of the Ded1-hyperdependent mRNAs identified in ded1 mutant cells exhibited strong TE reductions in glucose-starved or heat-shocked WT cells, and those down-regulated by glucose starvation also exhibited hyper-dependence on initiation factor eIF4B, and to a lesser extent eIF4A, for efficient translation in non-stressed cells. These findings are consistent with recent proposals that the dissociation of Ded1 from mRNA 5′UTRs and the condensation of Ded1 contribute to reduced Ded1 function during stress, and they further suggest that the down-regulation of eIF4B and eIF4A functions also contributes to the translational impairment of a select group of Ded1 mRNA targets with heightened dependence on all three factors during glucose starvation. Full article
(This article belongs to the Special Issue Yeast: Translation Regulation and Localized Translation)
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17 pages, 1480 KiB  
Article
Growth Inhibition by Amino Acids in Saccharomyces cerevisiae
by Stephanie J. Ruiz, Joury S. van ’t Klooster, Frans Bianchi and Bert Poolman
Microorganisms 2021, 9(1), 7; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9010007 - 22 Dec 2020
Cited by 18 | Viewed by 3882
Abstract
Amino acids are essential metabolites but can also be toxic when present at high levels intracellularly. Substrate-induced downregulation of amino acid transporters in Saccharomyces cerevisiae is thought to be a mechanism to avoid this toxicity. It has been shown that unregulated uptake by [...] Read more.
Amino acids are essential metabolites but can also be toxic when present at high levels intracellularly. Substrate-induced downregulation of amino acid transporters in Saccharomyces cerevisiae is thought to be a mechanism to avoid this toxicity. It has been shown that unregulated uptake by the general amino acid permease Gap1 causes cells to become sensitive to amino acids. Here, we show that overexpression of eight other amino acid transporters (Agp1, Bap2, Can1, Dip5, Gnp1, Lyp1, Put4, or Tat2) also induces a growth defect when specific single amino acids are present at concentrations of 0.5–5 mM. We can now state that all proteinogenic amino acids, as well as the important metabolite ornithine, are growth inhibitory to S. cerevisiae when transported into the cell at high enough levels. Measurements of initial transport rates and cytosolic pH show that toxicity is due to amino acid accumulation and not to the influx of co-transported protons. The amino acid sensitivity phenotype is a useful tool that reports on the in vivo activity of transporters and has allowed us to identify new transporter-specific substrates. Full article
(This article belongs to the Special Issue Yeast: Translation Regulation and Localized Translation)
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Review

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12 pages, 1047 KiB  
Review
Seeking a Role for Translational Control by Alternative Polyadenylation in Saccharomyces cerevisiae
by Rachael E. Turner and Traude H. Beilharz
Microorganisms 2021, 9(9), 1885; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9091885 - 05 Sep 2021
Cited by 1 | Viewed by 2310
Abstract
Alternative polyadenylation (APA) represents an important mechanism for regulating isoform-specific translation efficiency, stability, and localisation. Though some progress has been made in understanding its consequences in metazoans, the role of APA in the model organism Saccharomyces cerevisiae remains a relative mystery because, despite [...] Read more.
Alternative polyadenylation (APA) represents an important mechanism for regulating isoform-specific translation efficiency, stability, and localisation. Though some progress has been made in understanding its consequences in metazoans, the role of APA in the model organism Saccharomyces cerevisiae remains a relative mystery because, despite abundant studies on the translational state of mRNA, none differentiate mRNA isoforms’ alternative 3′-end. This review discusses the implications of alternative polyadenylation in S. cerevisiae using other organisms to draw inferences. Given the foundational role that research in this yeast has played in the discovery of the mechanisms of cleavage and polyadenylation and in the drivers of APA, it is surprising that such an inference is required. However, because advances in ribosome profiling are insensitive to APA, how it impacts translation is still unclear. To bridge the gap between widespread observed APA and the discovery of any functional consequence, we also provide a review of the experimental techniques used to uncover the functional importance of 3′ UTR isoforms on translation. Full article
(This article belongs to the Special Issue Yeast: Translation Regulation and Localized Translation)
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22 pages, 1180 KiB  
Review
Iron in Translation: From the Beginning to the End
by Antonia María Romero, María Teresa Martínez-Pastor and Sergi Puig
Microorganisms 2021, 9(5), 1058; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9051058 - 13 May 2021
Cited by 6 | Viewed by 3111
Abstract
Iron is an essential element for all eukaryotes, since it acts as a cofactor for many enzymes involved in basic cellular functions, including translation. While the mammalian iron-regulatory protein/iron-responsive element (IRP/IRE) system arose as one of the first examples of translational regulation in [...] Read more.
Iron is an essential element for all eukaryotes, since it acts as a cofactor for many enzymes involved in basic cellular functions, including translation. While the mammalian iron-regulatory protein/iron-responsive element (IRP/IRE) system arose as one of the first examples of translational regulation in higher eukaryotes, little is known about the contribution of iron itself to the different stages of eukaryotic translation. In the yeast Saccharomyces cerevisiae, iron deficiency provokes a global impairment of translation at the initiation step, which is mediated by the Gcn2-eIF2α pathway, while the post-transcriptional regulator Cth2 specifically represses the translation of a subgroup of iron-related transcripts. In addition, several steps of the translation process depend on iron-containing enzymes, including particular modifications of translation elongation factors and transfer RNAs (tRNAs), and translation termination by the ATP-binding cassette family member Rli1 (ABCE1 in humans) and the prolyl hydroxylase Tpa1. The influence of these modifications and their correlation with codon bias in the dynamic control of protein biosynthesis, mainly in response to stress, is emerging as an interesting focus of research. Taking S. cerevisiae as a model, we hereby discuss the relevance of iron in the control of global and specific translation steps. Full article
(This article belongs to the Special Issue Yeast: Translation Regulation and Localized Translation)
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