First Author | Aparisi Rey A | Year | 2019 |
Journal | EMBO Rep | Volume | 20 |
Issue | 6 | PubMed ID | 30948457 |
Mgi Jnum | J:276893 | Mgi Id | MGI:6315704 |
Doi | 10.15252/embr.201846022 | Citation | Aparisi Rey A, et al. (2019) Gadd45alpha modulates aversive learning through post-transcriptional regulation of memory-related mRNAs. EMBO Rep 20(6) |
abstractText | Learning is essential for survival and is controlled by complex molecular mechanisms including regulation of newly synthesized mRNAs that are required to modify synaptic functions. Despite the well-known role of RNA-binding proteins (RBPs) in mRNA functionality, their detailed regulation during memory consolidation is poorly understood. This study focuses on the brain function of the RBP Gadd45alpha (growth arrest and DNA damage-inducible protein 45 alpha, encoded by the Gadd45a gene). Here, we find that hippocampal memory and long-term potentiation are strongly impaired in Gadd45a-deficient mice, a phenotype accompanied by reduced levels of memory-related mRNAs. The majority of the Gadd45alpha-regulated transcripts show unusually long 3' untranslated regions (3'UTRs) that are destabilized in Gadd45a-deficient mice via a transcription-independent mechanism, leading to reduced levels of the corresponding proteins in synaptosomes. Moreover, Gadd45alpha can bind specifically to these memory-related mRNAs. Our study reveals a new function for extended 3'UTRs in memory consolidation and identifies Gadd45alpha as a novel regulator of mRNA stability. |