The team, led by Timothy Bredy, UCI associate professor of neurobiology & behavior, discovered that chemical modifications that add methyl groups to RNA, a process known as methylation, could strengthen memory formation.  Results appear June 22 in the Journal of Neuroscience.

The modification of RNA by methylation can affect how it functions within a cell. When the researchers reduced the brain levels of an enzyme that removes methyl groups from RNA, the result was a boost in memory formation.

“By genetically silencing an enzyme in a specific region of the brain involved in memory and adaptive behavior, we saw much better memory recall in mice,” said Jocelyn Widagdo, postdoctoral fellow and co-lead author of the study from the Queensland Brain Institute in Australia.

To investigate the possible role of RNA methylation in the formation of new memories, Bredy and his colleagues searched the entire genome for methylated RNA in brain tissue from mice recently trained on a learning task. They found widespread changes in a recently identified epigenetic mark, N6-methyladenosine (m6A), on RNA when new memories were formed. Epigenetic processes are believed to be the molecular link between our genes and the environment, such as during learning.

“Our findings show that memory processing is not just influenced by epigenetic control over our DNA but also occur at the level of RNA, variations in which act like a messenger in our cells,” said Bredy. “m6A shows enormous potential because the process can rapidly fine-tune our gene function and expression, which is often impaired in a variety of neurological disorders.”

According to the researchers, a next step would be for them to determine what happens to the process during other forms of learning, and whether the network is disrupted in memory-related disorders such as post-traumatic stress disorder or phobia.

Other researchers who contributed to this work are Qiongyi Zhao, Marie-Jeanne Kempen, Men Chee Tan, Vikram Ratnu, Wei Wei, Laura Leighton, Paola Spadaro, Janette Edson and Victor Anggono from the University of Queensland.  The research was supported by the National Institutes of Mental Health (grant 1R01MH109588-01), the Australian National Health and Medical Research Council (APP1042051, APP1062570 and 477108), the Australian Research Council (DP1096148) and the John T. Reid Charitable Trust.

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