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  1. Article ; Online: Correction: Computational analysis of the oscillatory behavior at the translation level induced by mRNA levels oscillations due to finite intracellular resources.

    Zarai, Yoram / Tuller, Tamir

    PLoS computational biology

    2019  Volume 15, Issue 7, Page(s) e1007192

    Abstract: This corrects the article DOI: 10.1371/journal.pcbi.1006055.]. ...

    Abstract [This corrects the article DOI: 10.1371/journal.pcbi.1006055.].
    Language English
    Publishing date 2019-07-02
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1007192
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Correction

    Yoram Zarai / Tamir Tuller

    PLoS Computational Biology, Vol 15, Iss 7, p e

    Computational analysis of the oscillatory behavior at the translation level induced by mRNA levels oscillations due to finite intracellular resources.

    2019  Volume 1007192

    Abstract: This corrects the article DOI:10.1371/journal.pcbi.1006055.]. ...

    Abstract [This corrects the article DOI:10.1371/journal.pcbi.1006055.].
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Computational analysis of the oscillatory behavior at the translation level induced by mRNA levels oscillations due to finite intracellular resources.

    Zarai, Yoram / Tuller, Tamir

    PLoS computational biology

    2018  Volume 14, Issue 4, Page(s) e1006055

    Abstract: Recent studies have demonstrated how the competition for the finite pool of available gene expression factors has important effect on fundamental gene expression aspects. In this study, based on a whole-cell model simulation of translation in S. ... ...

    Abstract Recent studies have demonstrated how the competition for the finite pool of available gene expression factors has important effect on fundamental gene expression aspects. In this study, based on a whole-cell model simulation of translation in S. cerevisiae, we evaluate for the first time the expected effect of mRNA levels fluctuations on translation due to the finite pool of ribosomes. We show that fluctuations of a single gene or a group of genes mRNA levels induce periodic behavior in all S. cerevisiae translation factors and aspects: the ribosomal densities and the translation rates of all S. cerevisiae mRNAs oscillate. We numerically measure the oscillation amplitudes demonstrating that fluctuations of endogenous and heterologous genes can cause a significant fluctuation of up to 50% in the steady-state translation rates of the rest of the genes. Furthermore, we demonstrate by synonymous mutations that oscillating the levels of mRNAs that experience high ribosomal occupancy (e.g. ribosomal "traffic jam") induces the largest impact on the translation of the S. cerevisiae genome. The results reported here should provide novel insights and principles related to the design of synthetic gene expression circuits and related to the evolutionary constraints shaping gene expression of endogenous genes.
    MeSH term(s) Amino Acid Substitution ; Codon/genetics ; Computational Biology ; Computer Simulation ; Evolution, Molecular ; Gene Expression ; Genes, Synthetic ; Genome, Fungal ; Green Fluorescent Proteins/biosynthesis ; Green Fluorescent Proteins/genetics ; Kinetics ; Models, Genetic ; Monte Carlo Method ; Protein Biosynthesis ; RNA, Fungal/genetics ; RNA, Fungal/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/genetics ; Ribosomes/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism
    Chemical Substances Codon ; RNA, Fungal ; RNA, Messenger ; Recombinant Proteins ; Green Fluorescent Proteins (147336-22-9)
    Language English
    Publishing date 2018-04-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1006055
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Computational analysis of the oscillatory behavior at the translation level induced by mRNA levels oscillations due to finite intracellular resources.

    Yoram Zarai / Tamir Tuller

    PLoS Computational Biology, Vol 14, Iss 4, p e

    2018  Volume 1006055

    Abstract: Recent studies have demonstrated how the competition for the finite pool of available gene expression factors has important effect on fundamental gene expression aspects. In this study, based on a whole-cell model simulation of translation in S. ... ...

    Abstract Recent studies have demonstrated how the competition for the finite pool of available gene expression factors has important effect on fundamental gene expression aspects. In this study, based on a whole-cell model simulation of translation in S. cerevisiae, we evaluate for the first time the expected effect of mRNA levels fluctuations on translation due to the finite pool of ribosomes. We show that fluctuations of a single gene or a group of genes mRNA levels induce periodic behavior in all S. cerevisiae translation factors and aspects: the ribosomal densities and the translation rates of all S. cerevisiae mRNAs oscillate. We numerically measure the oscillation amplitudes demonstrating that fluctuations of endogenous and heterologous genes can cause a significant fluctuation of up to 50% in the steady-state translation rates of the rest of the genes. Furthermore, we demonstrate by synonymous mutations that oscillating the levels of mRNAs that experience high ribosomal occupancy (e.g. ribosomal "traffic jam") induces the largest impact on the translation of the S. cerevisiae genome. The results reported here should provide novel insights and principles related to the design of synthetic gene expression circuits and related to the evolutionary constraints shaping gene expression of endogenous genes.
    Keywords Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2018-04-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Correction: On the Ribosomal Density that Maximizes Protein Translation Rate.

    Zarai, Yoram / Margaliot, Michael / Tuller, Tamir

    PloS one

    2017  Volume 12, Issue 5, Page(s) e0177650

    Abstract: This corrects the article DOI: 10.1371/journal.pone.0166481.]. ...

    Abstract [This corrects the article DOI: 10.1371/journal.pone.0166481.].
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0177650
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Ribosome flow model with extended objects.

    Zarai, Yoram / Margaliot, Michael / Tuller, Tamir

    Journal of the Royal Society, Interface

    2017  Volume 14, Issue 135

    Abstract: We study a deterministic mechanistic model for the flow of ribosomes along the mRNA molecule, called ... ...

    Abstract We study a deterministic mechanistic model for the flow of ribosomes along the mRNA molecule, called the
    MeSH term(s) Models, Biological ; Protein Biosynthesis/physiology ; RNA, Messenger/chemistry ; RNA, Messenger/metabolism ; Ribosomes/chemistry ; Ribosomes/metabolism
    Chemical Substances RNA, Messenger
    Language English
    Publishing date 2017-10-11
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 2156283-0
    ISSN 1742-5662 ; 1742-5689
    ISSN (online) 1742-5662
    ISSN 1742-5689
    DOI 10.1098/rsif.2017.0128
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: eIF3 mRNA selectivity profiling reveals eIF3k as a cancer-relevant regulator of ribosome content.

    Duan, Haoran / Zhang, Siqiong / Zarai, Yoram / Öllinger, Rupert / Wu, Yanmeng / Sun, Li / Hu, Cheng / He, Yaohui / Tian, Guiyou / Rad, Roland / Kong, Xiangquan / Cheng, Yabin / Tuller, Tamir / Wolf, Dieter A

    The EMBO journal

    2023  Volume 42, Issue 12, Page(s) e112362

    Abstract: eIF3, whose subunits are frequently overexpressed in cancer, regulates mRNA translation from initiation to termination, but mRNA-selective functions of individual subunits remain poorly defined. Using multiomic profiling upon acute depletion of eIF3 ... ...

    Abstract eIF3, whose subunits are frequently overexpressed in cancer, regulates mRNA translation from initiation to termination, but mRNA-selective functions of individual subunits remain poorly defined. Using multiomic profiling upon acute depletion of eIF3 subunits, we observed that while eIF3a, b, e, and f markedly differed in their impact on eIF3 holo-complex formation and translation, they were each required for cancer cell proliferation and tumor growth. Remarkably, eIF3k showed the opposite pattern with depletion promoting global translation, cell proliferation, tumor growth, and stress resistance through repressing the synthesis of ribosomal proteins, especially RPS15A. Whereas ectopic expression of RPS15A mimicked the anabolic effects of eIF3k depletion, disruption of eIF3 binding to the 5'-UTR of RSP15A mRNA negated them. eIF3k and eIF3l are selectively downregulated in response to endoplasmic reticulum and oxidative stress. Supported by mathematical modeling, our data uncover eIF3k-l as a mRNA-specific module which, through controlling RPS15A translation, serves as a rheostat of ribosome content, possibly to secure spare translational capacity that can be mobilized during stress.
    MeSH term(s) Humans ; Eukaryotic Initiation Factor-3/genetics ; Eukaryotic Initiation Factor-3/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Ribosomes/genetics ; Ribosomes/metabolism ; Ribosomal Proteins/genetics ; Ribosomal Proteins/metabolism ; Neoplasms/genetics ; Neoplasms/metabolism ; Protein Biosynthesis
    Chemical Substances Eukaryotic Initiation Factor-3 ; RNA, Messenger ; Ribosomal Proteins
    Language English
    Publishing date 2023-05-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.15252/embj.2022112362
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    In stock of ZB MED Cologne/Königswinter

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  8. Article ; Online: Networks of ribosome flow models for modeling and analyzing intracellular traffic.

    Nanikashvili, Itzik / Zarai, Yoram / Ovseevich, Alexander / Tuller, Tamir / Margaliot, Michael

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 1703

    Abstract: The ribosome flow model with input and output (RFMIO) is a deterministic dynamical system that has been used to study the flow of ribosomes during mRNA translation. The input of the RFMIO controls its initiation rate and the output represents the ... ...

    Abstract The ribosome flow model with input and output (RFMIO) is a deterministic dynamical system that has been used to study the flow of ribosomes during mRNA translation. The input of the RFMIO controls its initiation rate and the output represents the ribosome exit rate (and thus the protein production rate) at the 3' end of the mRNA molecule. The RFMIO and its variants encapsulate important properties that are relevant to modeling ribosome flow such as the possible evolution of "traffic jams" and non-homogeneous elongation rates along the mRNA molecule, and can also be used for studying additional intracellular processes such as transcription, transport, and more. Here we consider networks of interconnected RFMIOs as a fundamental tool for modeling, analyzing and re-engineering the complex mechanisms of protein production. In these networks, the output of each RFMIO may be divided, using connection weights, between several inputs of other RFMIOs. We show that under quite general feedback connections the network has two important properties: (1) it admits a unique steady-state and every trajectory converges to this steady-state; and (2) the problem of how to determine the connection weights so that the network steady-state output is maximized is a convex optimization problem. These mathematical properties make these networks highly suitable as models of various phenomena: property (1) means that the behavior is predictable and ordered, and property (2) means that determining the optimal weights is numerically tractable even for large-scale networks. For the specific case of a feed-forward network of RFMIOs we prove an additional useful property, namely, that there exists a spectral representation for the network steady-state, and thus it can be determined without any numerical simulations of the dynamics. We describe the implications of these results to several fundamental biological phenomena and biotechnological objectives.
    MeSH term(s) Algorithms ; Models, Biological ; Protein Biosynthesis ; RNA, Messenger/genetics ; Ribosomes/metabolism
    Chemical Substances RNA, Messenger
    Language English
    Publishing date 2019-02-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-018-37864-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Correction

    Yoram Zarai / Michael Margaliot / Tamir Tuller

    PLoS ONE, Vol 12, Iss 5, p e

    On the Ribosomal Density that Maximizes Protein Translation Rate.

    2017  Volume 0177650

    Abstract: This corrects the article DOI:10.1371/journal.pone.0166481.]. ...

    Abstract [This corrects the article DOI:10.1371/journal.pone.0166481.].
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Correction

    Yoram Zarai / Michael Margaliot / Tamir Tuller

    PLoS ONE, Vol 12, Iss 5, p e

    On the Ribosomal Density that Maximizes Protein Translation Rate.

    2017  Volume 0177650

    Abstract: This corrects the article DOI:10.1371/journal.pone.0166481.]. ...

    Abstract [This corrects the article DOI:10.1371/journal.pone.0166481.].
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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