Post-transcriptional mechanisms in synaptic plasticity and memory consolidation: Role of mRNA stability
German Resilience Center (DRZ) gGmbH, Mainz, Germany
Learning is essential for survival, and is regulated by complex molecular mechanisms including regulation of newly synthesized mRNAs that are required to modify synaptic functions. Despite of the well-known role of RNA-binding proteins (RBPs) in mRNA turnover, their detailed regulation during memory consolidation is poorly understood. This study focuses on the brain function of the RBP Gadd45α (Growth arrest and DNA damage-inducible protein 45 alpha). Here, we found that hippocampal memory and long-term potentiation were strongly impaired in Gadd45a-deficient mice, a phenotype accompanied by reduced levels of memory-related mRNAs. The majority of the Gadd45α-regulated transcripts showed unusually long 3´ untranslated regions (3'UTRs) that were destabilized in Gadd45a-deficient mice via a transcription-independent mechanism, leading to reduced levels of the corresponding proteins in synaptosomes. Moreover, Gadd45α can bind specifically to these memory-related mRNAs. Our study reveals a new function for extended 3'UTRs in memory consolidation and identifies Gadd45α as a novel regulator of mRNA stability.
Host: Susana Mato