"Quite different molecular machineries, widely conserved from sea slugs to rodents, are thought to underlie these two components. While modifications of pre-existing proteins are sufficient for the transient changes, new gene expression is required for those that are sustained," the researchers said, emphasizing that a gene's expression depends on both its transcription into messenger RNA and the translation of that messenger RNA into functional proteins.
Sonenberg and Costa-Mattioli earlier found the first genetic evidence that control over protein synthesis plays an important role in the formation of lasting memories.
"Most of the focus on gene control is at the level of transcription," Sonenberg said. "In contrast, here there is control at the level of translation—in making protein from messenger RNA, a less appreciated mode of regulation."
When the regulatory protein eIF2a is chemically modified with the addition of a phosphate to one of its amino acids, it switches on the protein synthesis of another factor that halts production of genes required for the long-term storage of memories. Sonenberg and his colleagues previously discovered that mice lacking the enzyme that performs the phosphorylation reaction have a superior ability to remember new things under certain training conditions.
“Those results led us to suspect that decreasing the phosphorylation of eIF2a enhanced memory storage,?Costa-Mattioli said.
In an effort to validate their earlier findings, the researchers have now generated mice carrying a version of eIF2a that cannot be phosphorylated. The mutant mice have lower levels of phosphorylated eIF2a and showed an improved talent for spatial learning in a water maze test.
In the test, the