Gadd45α Modulates Aversive Learning Through Post-transcriptional Regulation of Memory-related MRNAs

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2019 Apr 6

PMID 30948457

Citations 7

Authors

Alejandro Aparisi Rey

Emil Karaulanov

Salim Sharopov

Khelifa Arab

Andrea Schafer

Mathias Gierl

Stephan Guggenhuber

Caroline Brandes

Luigi Pennella

Wolfram H Gruhn

Ruth Jelinek

Christina Maul

Andrea Conrad

Werner Kilb

Heiko J Luhmann

Christof Niehrs

Beat Lutz

Affiliations

Soon will be listed here.

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 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 gene). Here, we find that hippocampal memory and long-term potentiation are strongly impaired in -deficient mice, a phenotype accompanied by reduced levels of memory-related mRNAs. The majority of the Gadd45αregulated transcripts show unusually long 3' untranslated regions (3'UTRs) that are destabilized in -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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