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Posttranscriptional regulation of gene expression in learning by the neuronal ELAV-like mRNA-stabilizing proteins

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Quattrone, Alessandro, Pascale, Alessia, Nogues, Xavier, Zhao, Weiqin, Gusev, Pavel, Pacini, Alessandra, Alkon, Daniel L.·2001·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.191388398PMC PMC58787
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Abstract

The view that memory is encoded by variations in the strength of synapses implies that long-term biochemical changes take place within subcellular microdomains of neurons. These changes are thought ultimately to be an effect of transcriptional regulation of specific genes. Localized changes, however, cannot be fully explained by a purely transcriptional control of gene expression. The neuron-specific ELAV-like HuB, HuC, and HuD RNA-binding proteins act posttranscriptionally by binding to adenine- and uridine-rich elements (AREs) in the 3′ untranslated region of a set of target mRNAs, and by increasing mRNA cytoplasmic stability and/or rate of translation. Here we show that neuronal ELAV-like genes undergo a sustained up-regulation in hippocampal pyramidal cells only of mice and rats that have learned a spatial discrimination paradigm. This learning-specific increase of ELAV-like proteins was localized within cytoplasmic compartments of the somata and proximal dendrites and was associated with the cytoskeleton. This increase was also accompanied by enhanced expression of the GAP-43 gene, known to be regulated mainly posttranscriptionally and whose mRNA is demonstrated here to be an in vivo ELAV-like target. Antisense-mediated knockdown of HuC impaired spatial learning performance in mice and induced a concomitant down-regulation of GAP-43 expression. Neuronal ELAV-like proteins could exert learning-induced posttranscriptional control of an array of target genes uniquely suited to subserve substrates of memory storage.

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  • Expression of nELAV proteins and GAP-43 mRNA increased in the cytoskeletal and membrane fractions of murine hippocampal neurons following spatial discrimination tasks.

    “The first studies to link HuD to learning and memory demonstrated that expression of nELAV proteins and GAP-43 mRNA increased in the cytoskeletal and membrane fractions of murine hippocampal neurons following spatial discrimination tasks (Quattrone et al. 2001; Pascale et al. 2004).”

    From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Quattrone et al. 2001

    The Results and Discussion report increased neuronal ELAV-like protein in the membrane and especially cytoskeletal fractions of hippocampi from radial-maze-trained mice. They also report learning-associated up-regulation of GAP-43 mRNA, but do not show that its increase occurred in those fractions; the fraction-specific finding concerns the proteins. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Quattrone, A., Pascale, A., Nogues, X., Zhao, W., Gusev, P., Pacini, A., & Alkon, D. L.
Affiliations
  • West Virginia University (US)
  • Blanchette Rockefeller Neurosciences Institute, West Virginia University at Johns Hopkins University, Rockville, MD 20850; Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892; Laboratory of Cognitive Neurosciences, University of Bordeaux I, Talence 33405, France; and Laboratory of Functional Morphology, Department of Anatomy, Histology and Forensic Medicine, University of Florence, Florence 50134, Italy
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2001-09-25
Volume
98
Issue
20
Pages
11668-11673
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.191388398
PMC
PMC58787
OpenAlex
W2001504986
Cited by
137
References
2
Citations by year
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FWCI
2.57
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Florence Research (University of Florence) (submittedVersion)
  • Institutional Research Information System (Università degli Studi di Trento) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
ELAV-like proteins, HuC, hubs, HUD, post-transcriptional regulation, mRNA stability, 3' untranslated region, RNA-binding proteins, spatial learning, memory storage, hippocampal pyramidal neurons, GAP-43, antisense knockdown, cytoskeleton, dendrites, synaptic plasticity
MeSH terms
ELAV-Like Protein 3, Animals, Binding Sites, Gene Expression Regulation, Hippocampus, Learning, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Neurons, Oligodeoxyribonucleotides, Ribonucleoproteins, RNA, Messenger, Transcription, Genetic, Blotting, Western, RNA-Binding Proteins, Rats, Wistar, In Situ Hybridization, Mice, Knockout, Maze Learning, GAP-43 Protein, Reverse Transcriptase Polymerase Chain Reaction, Mice, Rats, ELAV Proteins

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