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Gadd45a modulates aversive learning through post-transcriptional regulation of memory-related mRNAs

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE100923 | GEO | 2019/04/01

REPOSITORIES: GEO

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Gadd45a promotes DNA demethylation through TDG

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2015-05-07 | E-GEOD-62496 | biostudies-arrayexpress

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Project description:Radiation biodosimetry based on transcriptomic analysis of peripheral blood is a valuable tool to detect radiation exposure after a radiological/nuclear event and obtain useful biological information that could predict tissue and organismal injury. However, confounding factors, including inflammation, can potentially obscure the predictive power of the method. The Gadd45 (growth arrest and DNA damage-inducible genes) family is composed of three members, Gadd45a, Gadd45b, and Gadd45g, that play important roles in cell growth control, differentiation, DNA repair, and apoptosis. Gadd45b and Gadd45g are important for inflammatory responses as well as mediating signals of the innate immune system, whereas Gadd45a is a negative regulator of activation-induced T cell proliferation. T cells from Gadd45a null mice are hyper-responsive to activating stimuli due to spontaneously increased p38MAPK activity. Importantly, Gadd45a-deficient mice develop an autoimmune disease, similar to human systemic lupus erythematosus, characterized by severe hematological disorders, kidney disease, and premature death. The goal of this study was to elucidate how pre-existing inflammatory condition in mice can affect radiation biodosimetry. We exposed wild-type and Gadd45a knockout C57BL/6J mice to 7 Gy x-rays and 24 h later we isolated whole blood and performed genome microarray and gene ontology analysis.

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miRNAs regulated by Gadd45a during somatic cell reprogramming

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Genes regulated by Gadd45a during somatic cell reprogramming

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