CUHK study reveals hidden role of brain-enriched circular RNA in memory Findings open new avenues for neurodegenerative disease research
A research team from The Chinese University of Hong Kong (CUHK)’s School of Biomedical Sciences in the Faculty of Medicine (CU Medicine) and the Gerald Choa Neuroscience Institute has made a breakthrough in understanding how circular ribonucleic acid (circular RNA) molecules contribute to the brain’s ability to form memories. Their findings, published in the international journal Science Advances, open new possibilities for future treatment of neurodegenerative diseases, including Alzheimer’s disease and amyotrophic lateral sclerosis (ALS).
Circular RNAs have close link to communication system in brain that forms memories
When we learn, neurons fire electrical signals at one another. With repeated learning, the receiving neurons become more sensitive, making them easier to catch the signal next time. To form a memory, our brain converts temporary electrical activity into lasting structural changes by building new proteins that strengthen and remodel the synapse – the bridge between neurons.
RNA is a biological molecule. In particular, messenger RNA (mRNA) carries genetic instructions from DNA to the parts of the cell that build proteins. RNA is usually single-stranded with two distinct ends, but there is a type of non-coding RNA where the ends are joined together to form a closed continuous loop and that is circular RNA. It is more resistant to being broken down. Studies have revealed that circular RNAs were once dismissed as meaningless by-products, have close links to synaptic function.
Depletion of circHomer1 impairs spatial learning and memory functions in mice
In the CUHK study, researchers identified circHomer1, a brain-enriched circular RNA derived from the Homer1 gene, as an essential regulator of synaptic function. They used the Barnes maze test to assess the spatial learning and memory performance of mice with reduced circHomer1, comparing them with control mice. Results showed that mice lacking circHomer1 took significantly longer to find the target hole and made more errors in locating it during the probe trial, compared to the controls.
Professor Jacque Ip
Professor Jacque Ip Pak-kan, Assistant Professor in the School of Biomedical Sciences at CU Medicine and Principal Investigator of the Gerald Choa Neuroscience Institute, said: “These behavioural impairments across multiple cognitive tasks indicate that circHomer1 is required for hippocampus-dependent spatial learning and memory.”
The team further revealed that circHomer1 acts as a molecular bridge that enables the transport of essential synaptic mRNAs to the dendrites of neurons. Losing circHomer1 weakens brain communication by deforming the dendritic spines, the “sockets” of synapses, and reducing the quantities of essential proteins they need to function.
Professor Ip explained: “Our discovery transforms our understanding of circular RNAs in health and disease. We have shown that circHomer1 is not a byproduct of transcription but a functional molecule whose decline directly contributes to synaptic failure.
“This study opens a completely new direction for the diagnosis and investigation of neurodegenerative disorders. Circulating circular RNAs could serve as biomarkers for neurological conditions. Additionally, restoring circHomer1 function could offer a distinct strategy for maintaining synaptic health and memory, even in the presence of other neuropathologies.”
circHomer1 acts as a molecular bridge that enables the transport of essential synaptic messenger RNAs (mRNAs) to the dendrites of neurons. Losing circHomer1 weakens brain communication by deforming the dendritic spines, the “sockets” of synapses, and reducing the quantities of essential proteins they need to function.
