News Release

New yeast prion helps cells survive

Prion proteins may be best known for their role in infectious diseases, but not all of them are destructive, new research shows

Peer-Reviewed Publication

RIKEN

Mod+ Yeast Contain Mod5 Aggregates

image: MOD+ yeast contain Mod5 aggregates (upper) and acquire resistance to an antifungal agent, fluconazole (lower). view more 

Credit: RIKEN

One of the greatest mysterious in cellular biology has been given a new twist thanks to findings reported in Science. Researchers at the RIKEN Brain Science Institute show that prions, proteins that transmit heritable information without DNA or RNA, can contribute to drug resistance and cellular adaptation. Their discovery of a yeast prion with these properties demonstrates the active role of the prion conversion in cellular fitness adaptation, providing new insights into the potentially broader function of prions in living organisms.

Since their discovery in the 1960s, the class of misfolded proteins known as prions has posed a fundamental challenge to the foundation of molecular biology: the idea that heritable information flows from DNA and RNA to protein, but never from protein to any other molecule. Contrary to this rule, prions are able to transmit information from one molecule to another through the transmission of their misfolded shape, with devastating consequences in diseases such as mad cow disease and Creutzfeldt-Jakob disease. The broader implications of this unusual transmission mechanism, however, are not well understood.

Among these implications, research on yeast prions has suggested that beyond their well-known role in diseases, some prions may confer survival advantages by helping organisms respond to environmental stress. To explore this idea, the BSI research team screened a wide range of different genes in budding yeast for previously-undiscovered prions. Out of 6000 genes screened, they found a new yeast prion protein "Mod5" with the unusual property that it lacks the glutamine and asparagine-rich amino acid sequences characteristic of other yeast prions. Sequences like these are thought to contribute to forming amyloid aggregates, the mechanism by which prions propagate.

Despite lacking these sequences, Mod5 forms amyloid aggregates just like other yeast prions. Unlike the destructive role such aggregates play in well-known prion diseases, however, the researchers showed that Mod5 aggregates actually help the yeast, by granting it cellular resistance to antifungal agents. This advantage is so important that the yeast actually increases prion conversion when the pressure is on, as the researchers found when they applied antifungal drugs to the yeast.

These results demonstrate that the Mod5 yeast prion contributes to cell survival under environmental stress, through selection playing a key role in evolutionary adaptation. This insight marks a breakthrough in our understanding of the evolutionary role of prions and their unique form of inheritance, promising new avenues in the battle to contain and treat some of the world's most dangerous infectious diseases.

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About RIKEN

RIKEN is Japan's flagship research institute devoted to basic and applied research. Over 2500 papers by RIKEN researchers are published every year in reputable scientific and technical journals, covering topics ranging across a broad spectrum of disciplines including physics, chemistry, biology, medical science and engineering. RIKEN's advanced research environment and strong emphasis on interdisciplinary collaboration has earned itself an unparalleled reputation for scientific excellence in Japan and around the world.

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About the Brain Science Institute

The RIKEN Brain Science Institute (BSI) was established as an institute at RIKEN in October, 1997 to answer a growing need in society for cutting-edge brain science research. Since its establishment, BSI has attracted promising scientists domestically and internationally and brought together diverse research and human resources, and today enjoys an international reputation as an innovative center for brain science.

Research at BSI integrates a wide range of disciplines including medicine, biology, physics, technology, information science, mathematical science, and psychology. BSI's research objectives cover individual organisms, behavior, microscopic molecular structures of the brain, neurons, neurocircuits, cognition, memory, learning, language acquisition, and robotics.


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