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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