Role of highly conserved pyrimidine-rich sequences in the 3′ untranslated region of the GAP-43 mRNA in mRNA stability and RNA-protein interactions

Kohn, Douglas T.; Tsai, Kao-Chung; Cansino, Victor V.; Neve, Rachael L.; Perrone‐Bizzozero, Nora I.

doi:10.1016/0169-328x(95)00239-o

Cited by 45 publications

(63 citation statements)

References 52 publications

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“…We found that the GAP-43 3Ј UTR is highly conserved and contains major determinants for mRNA instability (Kohn et al, 1996a). Unlike such determinants in other post-transcriptionally regulated mRNAs (Shaw and Kamen, 1986;Shyu et al, 1991), these sequences do not contain AUUUA motifs but exhibit multiple U-rich stretches.…”

mentioning

confidence: 87%

“…As in previous studies, mRNA stability assays were performed in the GAP-43-deficient cell clone PC12-N36 (Kohn et al, 1996a). This line does not express detectable levels of the GAP-43 mRNA or protein (Perrone-Bizzozero et al, 1994).…”

Section: Cell Culture and Transfection Studiesmentioning

confidence: 99%

“…Studies on the stability of the various mRNAs were performed as described by Kohn et al (1996a). Once cultures reached 75-85% confluency, cells were induced for 16 hr in the presence of 5 M CdCl 2 .…”

Section: Mrna Stability Analysismentioning

confidence: 99%

“…Unlike such determinants in other post-transcriptionally regulated mRNAs (Shaw and Kamen, 1986;Shyu et al, 1991), these sequences do not contain AUUUA motifs but exhibit multiple U-rich stretches. We recently have shown that these U-rich regions contain recognition sites for three brainspecific RNA-binding proteins (Kohn et al, 1996a). The finding that their binding activity and the levels of the GAP-43 mRNA are correlated spatially and temporally further suggests that these proteins may be involved in the post-transcriptional regulation of GAP-43 gene expression (Kohn et al, 1996a).…”

mentioning

confidence: 99%

“…We recently have shown that these U-rich regions contain recognition sites for three brainspecific RNA-binding proteins (Kohn et al, 1996a). The finding that their binding activity and the levels of the GAP-43 mRNA are correlated spatially and temporally further suggests that these proteins may be involved in the post-transcriptional regulation of GAP-43 gene expression (Kohn et al, 1996a).…”

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confidence: 99%

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

et al. 1997

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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 3Ј untranslated region (3Ј UTR) of the mRNA. To map the sequences in the GAP-43 3Ј UTR that mediate this post-transcriptional event, we generated specific 3Ј UTR deletion mutants and chimeras with the ␤-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 5Ј and 3Ј ends of the GAP-43 3Ј UTR. Of these destabilizing elements, only the one at the 3Ј end is required for the stabilization of the mRNA in response to treatment with the phorbol ester TPA. This 3Ј UTR element consists of highly conserved uridine-rich sequences and contains specific recognition sites for two neural-specific GAP-43 mRNAbinding proteins. Analysis of the levels of mRNA and protein derived from various 3Ј 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 3Ј UTR of the GAP-43 mRNA. Given that, like the GAP-43 mRNA, its degradation machinery and the GAP-43 mRNAbinding proteins are expressed primarily in neural cells, we propose that these factors may be involved in the posttranscriptional regulation of GAP-43 gene expression during neuronal differentiation.

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confidence: 87%

Section: Cell Culture and Transfection Studiesmentioning

confidence: 99%

Section: Mrna Stability Analysismentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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

et al. 1997

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Comparative distribution of myristoylated alanine-rich C kinase substrate (MARCKS) and F1/GAP-43 gene expression in the adult rat brain

McNamara

Lenox

1997

J. Comp. Neurol.

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Myristoylated alanine-rich C-kinase substrate (MARCKS) and F1/GAP-43 (B-50/neuromodulin) are both major specific substrates for protein kinase C (PKC) and appear to play an important role in the regulation of neuroplastic events during development and in the adult brain. Since PKC isozymes are differentially expressed in brain and the expression of F1/GAP-43 and MARCKS are differentially regulated by PKC through posttranslational mechanisms, the present study examined the relative distribution of both mRNAs in the adult brain by using in situ hybridization histochemistry. MARCKS hybridization was most pronounced in the olfactory bulb, piriform cortex (layer II), medial habenular nucleus, subregions of the amygdala, specific hypothalamic nuclei, hippocampal granule cells, neocortex, and cerebellar cortex, intermediate in the superior colliculus, hippocampal CA1, and certain brainstem nuclei including the locus coeruleus, and low-absent in regions of the caudate-putamen, geniculate, thalamic nuclei, lateral habenular nucleus, and hippocampal CA3 pyramidal and hilar neurons. Consistent with previous reports, prominent F1/GAP-43 hybridization was observed in neocortex, medial geniculate, piriform cortex (layer II), substantia nigra pars compacta, hippocampal CA3 pyramidal cells, thalamic and hypothalamic nuclei, lateral habenular nucleus, locus coeruleus, raphe nuclei, and cerebellar granule cells, intermediate in regions of the thalamus, hypothalamus, and amygdala, and low-absent in regions of the olfactory bulb, caudate-putamen, medial habenular nucleus, hippocampal granule cells, and superior colliculus. Overall, F1/GAP-43 was highly expressed in a greater number of regions compared to MARCKS and, in a number of regions, including the hippocampus, habenular complex, ventral tegmentum, geniculate, and certain brain stem nuclei, a striking inverse pattern of expression was observed. These results indicate that MARCKS gene expression, like that of F1/GAP-43, remains elevated in select regions of the adult rat brain which are associated with a high degree of retained plasticity. The potential role of PKC in the regulation of MARCKS and F1/GAP-43 gene expression in brain is assessed.

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Activity-dependent regulation of axonal growth: Posttranscriptional control of the GAP-43 gene by the NMDA receptor in developing hippocampus

Cantallops

Routtenberg

1999

J. Neurobiol.

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Role of highly conserved pyrimidine-rich sequences in the 3′ untranslated region of the GAP-43 mRNA in mRNA stability and RNA-protein interactions

Cited by 45 publications

References 52 publications

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

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

Comparative distribution of myristoylated alanine-rich C kinase substrate (MARCKS) and F1/GAP-43 gene expression in the adult rat brain

Activity-dependent regulation of axonal growth: Posttranscriptional control of the GAP-43 gene by the NMDA receptor in developing hippocampus

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