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Regulatory mechanisms for 3'-end alternative splicing and polyadenylation of the Glial Fibrillary Acidic Protein, GFAP, transcript.
Nucleic Acids Res. 2007; 35(22):7636-50.NA

Abstract

The glial fibrillary acidic protein, GFAP, forms the intermediate cytoskeleton in cells of the glial lineage. Besides the common GFAP alpha transcript, the GFAP epsilon and GFAP kappa transcripts are generated by alternative mRNA 3'-end processing. Here we use a GFAP minigene to characterize molecular mechanisms participating in alternative GFAP expression. Usage of a polyadenylation signal within the alternatively spliced exon 7a is essential to generate the GFAP kappa and GFAP kappa transcripts. The GFAP kappa mRNA is distinct from GFAP epsilon mRNA given that it also includes intron 7a. Polyadenylation at the exon 7a site is stimulated by the upstream splice site. Moreover, exon 7a splice enhancer motifs supported both exon 7a splicing and polyadenylation. SR proteins increased the usage of the exon 7a polyadenylation signal but not the exon 7a splicing, whereas the polypyrimidine tract binding (PTB) protein enhanced both exon 7a polyadenylation and exon 7a splicing. Finally, increasing transcription by the VP16 trans-activator did not affect the frequency of use of the exon 7a polyadenylation signal whereas the exon 7a splicing frequency was decreased. Our data suggest a model with the selection of the exon 7a polyadenylation site being the essential and primary event for regulating GFAP alternative processing.

Authors+Show Affiliations

Institute of Human Genetics, The Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17981838

Citation

Blechingberg, Jenny, et al. "Regulatory Mechanisms for 3'-end Alternative Splicing and Polyadenylation of the Glial Fibrillary Acidic Protein, GFAP, Transcript." Nucleic Acids Research, vol. 35, no. 22, 2007, pp. 7636-50.
Blechingberg J, Lykke-Andersen S, Jensen TH, et al. Regulatory mechanisms for 3'-end alternative splicing and polyadenylation of the Glial Fibrillary Acidic Protein, GFAP, transcript. Nucleic Acids Res. 2007;35(22):7636-50.
Blechingberg, J., Lykke-Andersen, S., Jensen, T. H., Jørgensen, A. L., & Nielsen, A. L. (2007). Regulatory mechanisms for 3'-end alternative splicing and polyadenylation of the Glial Fibrillary Acidic Protein, GFAP, transcript. Nucleic Acids Research, 35(22), 7636-50.
Blechingberg J, et al. Regulatory Mechanisms for 3'-end Alternative Splicing and Polyadenylation of the Glial Fibrillary Acidic Protein, GFAP, Transcript. Nucleic Acids Res. 2007;35(22):7636-50. PubMed PMID: 17981838.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulatory mechanisms for 3'-end alternative splicing and polyadenylation of the Glial Fibrillary Acidic Protein, GFAP, transcript. AU - Blechingberg,Jenny, AU - Lykke-Andersen,Søren, AU - Jensen,Torben Heick, AU - Jørgensen,Arne Lund, AU - Nielsen,Anders Lade, Y1 - 2007/11/02/ PY - 2007/11/6/pubmed PY - 2008/1/19/medline PY - 2007/11/6/entrez SP - 7636 EP - 50 JF - Nucleic acids research JO - Nucleic Acids Res VL - 35 IS - 22 N2 - The glial fibrillary acidic protein, GFAP, forms the intermediate cytoskeleton in cells of the glial lineage. Besides the common GFAP alpha transcript, the GFAP epsilon and GFAP kappa transcripts are generated by alternative mRNA 3'-end processing. Here we use a GFAP minigene to characterize molecular mechanisms participating in alternative GFAP expression. Usage of a polyadenylation signal within the alternatively spliced exon 7a is essential to generate the GFAP kappa and GFAP kappa transcripts. The GFAP kappa mRNA is distinct from GFAP epsilon mRNA given that it also includes intron 7a. Polyadenylation at the exon 7a site is stimulated by the upstream splice site. Moreover, exon 7a splice enhancer motifs supported both exon 7a splicing and polyadenylation. SR proteins increased the usage of the exon 7a polyadenylation signal but not the exon 7a splicing, whereas the polypyrimidine tract binding (PTB) protein enhanced both exon 7a polyadenylation and exon 7a splicing. Finally, increasing transcription by the VP16 trans-activator did not affect the frequency of use of the exon 7a polyadenylation signal whereas the exon 7a splicing frequency was decreased. Our data suggest a model with the selection of the exon 7a polyadenylation site being the essential and primary event for regulating GFAP alternative processing. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/17981838/Regulatory_mechanisms_for_3'_end_alternative_splicing_and_polyadenylation_of_the_Glial_Fibrillary_Acidic_Protein_GFAP_transcript_ L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkm931 DB - PRIME DP - Unbound Medicine ER -