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Status |
Public on Apr 01, 2019 |
Title |
Gadd45a modulates aversive learning through post-transcriptional regulation of memory-related mRNAs |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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 of 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 Gadd45α (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 Gadd45α-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, 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.
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Overall design |
Gene expression profiling by RNA-seq of hippocampi from wild type and Gadd45a-knockout mice subjected to the passive avoidance (PA) test
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Contributor(s) |
Aparisi Rey A, Karaulanov E, Niehrs C, Lutz B |
Citation(s) |
30948457 |
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Submission date |
Jul 07, 2017 |
Last update date |
Jul 25, 2021 |
Contact name |
Emil Karaulanov |
Organization name |
Institute of Molecular Biology
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Lab |
Bioinformatics Core Facility
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Street address |
Ackermannweg 4
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City |
Mainz |
ZIP/Postal code |
55128 |
Country |
Germany |
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Platforms (1) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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Samples (12)
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Relations |
BioProject |
PRJNA393439 |
SRA |
SRP111344 |