KAIST's Professor Yoon Gi-jun and his research team have discovered the molecular mechanism by which neurons accurately transport specific ribonucleic acid (RNA) to the end of their axons. They found that the chemical marker 'm6A' serves as a 'delivery tag' that helps select the necessary RNA.
On September 14, KAIST announced that the research team identified the role of the m6A chemical modification in the process of transporting specific RNA to the end of the axon, a long pathway in neurons. The findings were published in the international journal 'Nature Communications' on July 30.
Neurons connect with other neurons through axons and dendrites that extend from the cell body. For the brain to develop and function normally, RNA produced at the cell center must be accurately delivered to the far ends of the neurons. However, the mechanisms for selecting and transporting specific RNA have not been fully understood.
The research team analyzed experimental mice in which the methylation enzyme that attaches m6A to RNA was inactive, confirming that the growth of dendrites was impaired. They then utilized a precise analysis technique called 'm6A-SAC-seq' to create a high-resolution map identifying the locations of m6A on RNA in the mouse brain, confirming that RNA necessary for axon growth is also marked with m6A.
The team also elucidated the process by which this marker is recognized and the RNA is transported. The protein 'YTHDF2' recognizes RNA with m6A, and together with the proteins 'FMRP' and 'KIF5C', it transports the RNA to the end of the neuron. Previously known primarily for aiding the degradation of unnecessary RNA, YTHDF2's involvement in RNA transport has been revealed through this study.
Previous research has reported associations between abnormalities in YTHDF2 and m6A regulation with neurodevelopmental disorders such as autism and degenerative brain diseases like Alzheimer's. The research team plans to conduct follow-up studies to explore the relationship between the newly identified concept of 'RNA delivery errors' and the failure to deliver normally produced RNA to necessary locations in relation to brain diseases. They are currently constructing a similar m6A map in human neurons, patient-derived iPSCs, and brain organoids.
This study involved KAIST students Koo Bon-sang and Hwang Hee-sun, along with Dr. Ajit Kumar as co-first authors. The research was supported by the Ministry of Science and ICT's Korean Research Foundation (NRF) New Research Program, the POSCO Cheongam Foundation, and the Seo Kyung-bae Science Foundation.
* This article has been translated by AI.
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