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Cited by 66RNA Research and SplicingRNA and protein synthesis mechanismsMolecular Biology Techniques and Applications

Post-Transcriptional Regulation of the GAP-43 Gene by Specific Sequences in the 3′ Untranslated Region of the mRNA

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Tsai, Kao-Chung, Cansino, Victor V., Kohn, Douglas T., Neve, Rachael L., Perrone-Bizzozero, Nora I.·1997·The Journal of Neuroscience
DOI 10.1523/jneurosci.17-06-01950.1997PMC PMC6793764
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Abstract

We have shown previously that GAP-43 gene expression during neuronal differentiation is controlled by selective changes in mRNA stability. This process was found to depend on highly conserved sequences in the 3′ untranslated region (3′ UTR) of the mRNA. To map the sequences in the GAP-43 3′ UTR that mediate this post-transcriptional event, we generated specific 3′ UTR deletion mutants and chimeras with the β-globin gene and measured their half-lives in transfected PC12 cells. Our results indicate that there are two distinct instability-conferring elements localized at the 5′ and 3′ ends of the GAP-43 3′ UTR. Of these destabilizing elements, only the one at the 3′ end is required for the stabilization of the mRNA in response to treatment with the phorbol ester TPA. This 3′ UTR element consists of highly conserved uridine-rich sequences and contains specific recognition sites for two neural-specific GAP-43 mRNA-binding proteins. Analysis of the levels of mRNA and protein derived from various 3′ UTR deletion mutants indicated that all mutants were translated effectively and that differences in gene expression in response to TPA were attributable to changes in GAP-43 mRNA stability. In addition, the phorbol ester was found to affect the binding of specific RNA-binding proteins to the 3′ UTR of the GAP-43 mRNA. Given that, like the GAP-43 mRNA, its degradation machinery and the GAP-43 mRNA-binding proteins are expressed primarily in neural cells, we propose that these factors may be involved in the post-transcriptional regulation of GAP-43 gene expression during neuronal differentiation.

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  • GAP-43 mRNA houses a class III ARE in its 3′ UTR.

    “Among all of the HuD-regulated mRNAs, the most prominent is the GAP-43 mRNA, which houses a class III ARE in its 3′ UTR (Chung et al. 1997; Tsai et al. 1997).”

    From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Tsai et al. 1997

    The Discussion (page not available) says the GAP-43 3′ UTR contains sequences resembling AU-rich elements, and the section on cis-acting elements identifies a U-rich instability determinant there. Our copy does not classify that element as a class III ARE, so it supports the location and general type of element but not the specific classification. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Tsai, K.-C., Cansino, V. V., Kohn, D. T., Neve, R. L., & Perrone-Bizzozero, N. I.
Affiliations
  • University of New Mexico (US)
  • Harvard University (US)
ORCID
Neve, Rachael L.
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
1997-03-15
Volume
17
Issue
6
Pages
1950-1958
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.17-06-01950.1997
PMC
PMC6793764
OpenAlex
W2166516791
Cited by
66
References
57
Citations by year
2023: 1 · 2020: 1 · 2017: 1 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 1
FWCI
2.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Tri-Service General Hospital
  • National Institutes of Health
  • School of Medicine, University of New Mexico
  • National Institute of Neurological Disorders and Stroke (NS 30255, R01NS030255)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD24236, P01HD024236)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
Keywords
GAP-43, 3' untranslated region, post-transcriptional regulation, mRNA stability, neuronal differentiation, mRNA-binding proteins, phorbol ester, tissue plasminogen activator, PC12 cells, gene expression regulation
MeSH terms
Animals, Cell Differentiation, Cells, Cultured, Membrane Glycoproteins, Nerve Tissue Proteins, RNA, Messenger, Transcription, Genetic, PC12 Cells, GAP-43 Protein, Rats

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