UNIST discovers circadian clock gene that regulates 24-hour sleep cycle

Discovery of genetic mutations in fruit flies that sleep less, revealing the principle

Professor Jongbin Lee and Jeonghoon Lim, Department of Life Sciences, UNIST

[울산과학기술원 제공. 재판매 및 DB 금지]

(Ulsan = Yonhap News) Reporter Kim Yong-tae = The Ulsan Institute of Science and Technology (UNIST) announced on the 22nd that it had discovered a new biological clock gene that regulates the 24-hour sleep cycle.

According to UNIST, a research team led by Professors Jong-bin Lee and Jeong-hoon Lim of the Department of Life Sciences discovered a mutation in the ‘Tango10’ (Transport and Golgi organization 10) gene in ‘Diligent Drosophila’, which sleeps abnormally, and identified the neurobiological principle.

When the Tango10 gene breaks down, the pacemaker neurons remain excited, disrupting the sleep cycle, the researchers explain.

Pacemaker neurons transmit 24-hour cycle information to other neurons in the brain so that all neurons have the same cycle.

The research team explained that the pacemaker neurons of the fruit fly, which had mutations in the Tango10 gene, had impaired ability to synchronize the biological clock.

In this fruit fly, there was no change in the shape of nerve endings that should be seen in a 24-hour cycle, and the Pigment-Dispersing Factor (PDF) neuropeptide, a substance secreted from nerve terminals to synchronize the biological clock of other cells, was also not normal.

PDF must be repeatedly accumulated and secreted in a 24-hour cycle, but in the Tango10 mutant, PDF continued to accumulate in nerve terminals.

The research team found that the Tango10 gene is involved in the function of these pacemaker neurons and sleep regulation by mediating protein ubiquitination (a process in which proteins are labeled by ubiquitin, a small protein composed of 76 amino acids).

To prove this, we found a Tango10-Cullin3 protein complex, which was accumulated at the end of the pacemaker nerve cell at a cycle of 24 hours.

Cullin3 is an enzyme widely known for attaching ubiquitin to proteins.

Professor Lim Jeong-hoon said, “If we find the target protein that is actually degraded by Tango10-Cullin3 and further investigate the relationship with human circadian sleep disorder, we will be able to find clues about the treatment of sleep disorders.”

The study was conducted in collaboration with Professor Ravi Alada of Northwestern University in the United States, and will be officially published in the Proceedings of the National Academy of Sciences (PNAS) of the United States on the 23rd.

The research was supported by the National Research Foundation of Korea’s Biomedical Technology Development Project and the Creative Challenge Research Foundation Support Project.

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