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Abstract:

Promoters and enhancers are cis-acting elements that control gene transcription via complex networks of protein-DNA and proteinprotein interactions. Whereas promoters deal with putting in place the RNA polymerase, both enhancers and promoters can control transcriptional initiation and elongation. We have previously shown that promoter structure modulates alternative splicing, strengthening the concept of a physical and functional coupling between transcription and splicing. Here we report that the promoter effect is due to the control of RNA pol II elongation. We found that the simian virus 40 (SV40) transcriptional enhancer, inserted in fibronectin (FN) minigene constructs transfected into mammalian cells, controls alternative splicing by inhibiting inclusion of the FN extra domain I (EDI) exon into mature mRNA. Deletion analysis of enhancer subdomains and competitions in vivo with excess of specific enhancer DNA subfragments demonstrate that the "minimal" enhancer, consisting of two 72-bp repeats, is responsible for the splicing effect. The 72-bp repeat region has been reported to promote RNA pol II elongation. When transcription is driven by the α-globin promoter linked to the SV40 enhancer, basal EDI inclusion and activation by the SR (Ser-Arg-rich) protein SF2/ASF are much lower than with other promoters. Deletion of only one of the two 72-bp repeats not only provokes higher EDI inclusion levels but allows responsiveness to SF2/ASF. These effects are the consequence of a decrease in RNA pol II elongation evidenced both by an increase in the proportions of shorter proximal over full length transcripts and by higher pol II densities upstream of the alternative exon detected by chromatin immunoprecipitation.

Registro:

Documento: Artículo
Título:Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation
Autor:Kadener, S.; Fededa, J.P.; Rosbash, M.; Kornblihtt, A.R.
Filiación:Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, Pabellón II (C1428EHA), Buenos Aires, Argentina
Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, United States
Palabras clave:Coupling; RNA processing; Transcription; alpha globin; cis acting element; fibronectin; RNA polymerase II; alternative RNA splicing; article; chromatin; enhancer region; exon; genetic transcription; genetic transfection; immunoprecipitation; in vivo study; priority journal; promoter region; protein DNA interaction; protein protein interaction; RNA processing; Simian virus 40; transcription initiation; transcription regulation; Alternative Splicing; Animals; Base Sequence; Cell Line; DNA Primers; Enhancer Elements (Genetics); Exons; Fibronectins; Gene Expression Regulation; Mammals; Models, Genetic; Polymerase Chain Reaction; RNA Polymerase II; Simian virus 40; Transcription, Genetic; Transfection; Mammalia; Simiae; Simian virus 40
Año:2002
Volumen:99
Número:12
Página de inicio:8185
Página de fin:8190
DOI: http://dx.doi.org/10.1073/pnas.122246099
Título revista:Proceedings of the National Academy of Sciences of the United States of America
Título revista abreviado:Proc. Natl. Acad. Sci. U. S. A.
ISSN:00278424
CODEN:PNASA
CAS:DNA Primers; Fibronectins; RNA Polymerase II, EC 2.7.7.-
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00278424_v99_n12_p8185_Kadener.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v99_n12_p8185_Kadener

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Citas:

---------- APA ----------
Kadener, S., Fededa, J.P., Rosbash, M. & Kornblihtt, A.R. (2002) . Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation. Proceedings of the National Academy of Sciences of the United States of America, 99(12), 8185-8190.
http://dx.doi.org/10.1073/pnas.122246099
---------- CHICAGO ----------
Kadener, S., Fededa, J.P., Rosbash, M., Kornblihtt, A.R. "Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation" . Proceedings of the National Academy of Sciences of the United States of America 99, no. 12 (2002) : 8185-8190.
http://dx.doi.org/10.1073/pnas.122246099
---------- MLA ----------
Kadener, S., Fededa, J.P., Rosbash, M., Kornblihtt, A.R. "Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation" . Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 12, 2002, pp. 8185-8190.
http://dx.doi.org/10.1073/pnas.122246099
---------- VANCOUVER ----------
Kadener, S., Fededa, J.P., Rosbash, M., Kornblihtt, A.R. Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation. Proc. Natl. Acad. Sci. U. S. A. 2002;99(12):8185-8190.
http://dx.doi.org/10.1073/pnas.122246099