• New micro-protein helps yeast cells cope

    From ScienceDaily@1:317/3 to All on Monday, March 07, 2022 21:30:50
    New micro-protein helps yeast cells cope with nutrient scarcity

    Date:
    March 7, 2022
    Source:
    University of Eastern Finland
    Summary:
    Researchers have discovered that a micro-protein, which they named
    Nrs1, supports cell division and proliferation when nutrients
    are scarce.



    FULL STORY ========================================================================== Researchers from the University of Eastern Finland and the University
    of Montreal (Canada) have discovered that a micro-protein, which they
    named Nrs1, supports cell division and proliferation when nutrients
    are scarce. This result, published in PLOS Biology last week, sheds a
    new light on how evolution subtly reshapes the genomes of unicellular microorganisms, providing them with plasticity to adjust their growth
    and proliferation to ever-changing environments.


    ==========================================================================
    At the turn of the millennium, scientists became able to experimentally determine the DNA sequence of entire genomes. They next used this
    information to predict genome products: the proteins.

    "At this time, very short DNA sections coding for very small proteins
    were overlooked. Why spend resources studying these tiny, shy dudes when there's already so much to do with the big, tough guys? This strategy
    paid off to identify central, evolutionary conserved cellular mechanisms;
    but the adaptation potential, though, hides in less conserved, often
    short DNA sequences," says University Researcher Sylvain Tollis who
    carried out the study in Montreal and at the Institute of Biomedicine, University of Eastern Finland.

    Furthermore, micro-proteins are increasingly associated with disease
    in humans: for instance, humanin, which is only 24 amino acids long, is involved in neuronal cell death and survival1, while the cancer-associated microprotein CASIMO1 promotes cell proliferation and motility in breast
    cancer cell lines through the actin cytoskeleton2. These results urge
    the community to scrutinize smaller proteins, or micro-proteins, and
    other genome sequences previously left aside.

    In the newly published study, the authors used the bakers' yeast
    Saccharomyces cerevisiae to seek for molecular routes by which the
    information on nutrient availability could be communicated to the key molecules, called transcription factors, that orchestrate the commitment
    to division, referred to as the Start point. Indeed, cell growth and
    division are strongly affected by the availability of nutrients. For
    this purpose, they deleted from the yeast genome the main activators
    of cell division, and overexpressed one by one the remainder of yeast
    proteins, including many small ones. A unique micro-protein emerged
    from this screen as capable of rescuing cell proliferation despite the
    absence of key cell division activators. Further biochemical analyses
    and ground-breaking quantitative microscopy investigations revealed that
    cells express this protein only under poor nitrogen conditions, and when
    it is time to divide. The authors have therefore renamed it as Nrs1 for Nitrogen- Responsive Start regulator. Nrs1 binds to and activates the
    main transcription factors that trigger the decision to divide, providing
    an alternative, nutrient-regulated mechanism for Start activation.

    Sequence analysis across yeast species indicated that Nrs1 is a recently- evolved microprotein, illustrating how microproteins can rapidly emerge
    to rewire fundamental cellular processes.

    "Indeed, it seems reasonable to assume that short DNA sequences
    would require less evolution-selected mutations than long sequences
    to be functionally optimized. This work raises the hypothesis that micro-proteins would make a versatile tool for evolution to quickly
    rewire key cellular pathways and provide plasticity to adapt to changing environment," Tollis concludes.

    This study was funded by the Canadian Institutes of Health Research,
    Genome Quebec and Genome Canada, and the Sigrid Juse'lius Foundation.

    References: 1: Gong Z, Tasset I, Diaz A, Anguiano J, Tas E, Cui L, et
    al. Humanin is an endogenous activator of chaperone-mediated autophagy.J
    Cell Biol. 2018;217(2): 635-47.

    2: Polycarpou-Schwarz M, Gross M, Mestdagh P, Schott J, Grund SE,
    Hildenbrand C, et al. The cancer-associated microprotein CASIMO1 controls
    cell proliferation and interacts with squalene epoxidase modulating
    lipid droplet formation. Oncogene. 2018;37(34):4750-68.

    ========================================================================== Story Source: Materials provided by University_of_Eastern_Finland. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Sylvain Tollis, Jaspal Singh, Roger Palou, Yogitha Thattikota, Ghada
    Ghazal, Jasmin Coulombe-Huntington, Xiaojing Tang, Susan Moore,
    Deborah Blake, Eric Bonneil, Catherine A. Royer, Pierre Thibault,
    Mike Tyers. The microprotein Nrs1 rewires the G1/S transcriptional
    machinery during nitrogen limitation in budding yeast. PLOS Biology,
    2022; 20 (3): e3001548 DOI: 10.1371/journal.pbio.3001548 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220307113134.htm

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