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Abstract:

Alternative splicing accounts for much of the complexity in higher eukaryotes. Thus, its regulation must allow for flexibility without hampering either its specificity or its fidelity. The mechanisms involved in alternative splicing regulation, especially those acting through coupling with transcription, have not been deeply studied in in vivo models. Much of our knowledge comes from in vitro approaches, where conditions can be precisely controlled at the expense of losing several levels of regulation present in intact cells. Here we studied the relative order of removal of the introns flanking a model alternative cassette exon. We show that there is a preferential removal of the intron downstream from the cassette exon before the upstream intron has been removed. Most importantly, both cis-acting mutations and trans-acting factors that regulate the model alternative splicing event differentially affect the relative order of removal. However, reduction of transcriptional elongation causing higher inclusion of the cassette exon does not change the order of intron removal, suggesting that the assumption, according to the "first come, first served" model, that slow elongation promotes preferential excision of the upstream intron has to be revised. We propose instead that slow elongation favors commitment to exon inclusion during spliceosome assembly. Our results reveal that measuring the order of intron removal may be a straightforward read-out to discriminate among different mechanisms of alternative splice site selection.

Registro:

Documento: Artículo
Título:First come, first served revisited: Factors affecting the same alternative splicing event have different effects on the relative rates of intron removal
Autor:De La Matta, M.; Lafaille, C.; Kornblihtt, A.R.
Filiación:Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular, y Celular (IFIBYNE-CONICET), Universidad de Buenos Aires, Pabellón 2, C1428EHA Buenos Aires, Argentina
Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
Palabras clave:Alternative splicing; Coupling; Order of intron removal; Pol II elongation; transcription elongation factor; alternative RNA splicing; article; exon; gene cassette; human; human cell; intron; mutation; priority journal; spliceosome; Alternative Splicing; Base Sequence; Cell Line; DNA Polymerase II; DNA Primers; Exons; Fibronectins; Humans; Introns; Kinetics; Models, Biological; Mutation; RNA Precursors; RNA Splice Sites; Transfection; Eukaryota
Año:2010
Volumen:16
Número:5
Página de inicio:904
Página de fin:912
DOI: http://dx.doi.org/10.1261/rna.1993510
Título revista:RNA
Título revista abreviado:RNA
ISSN:13558382
CODEN:RNARF
CAS:DNA Polymerase II, 2.7.7.-; DNA Primers; Fibronectins; RNA Precursors; RNA Splice Sites
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13558382_v16_n5_p904_DeLaMatta

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Citas:

---------- APA ----------
De La Matta, M., Lafaille, C. & Kornblihtt, A.R. (2010) . First come, first served revisited: Factors affecting the same alternative splicing event have different effects on the relative rates of intron removal. RNA, 16(5), 904-912.
http://dx.doi.org/10.1261/rna.1993510
---------- CHICAGO ----------
De La Matta, M., Lafaille, C., Kornblihtt, A.R. "First come, first served revisited: Factors affecting the same alternative splicing event have different effects on the relative rates of intron removal" . RNA 16, no. 5 (2010) : 904-912.
http://dx.doi.org/10.1261/rna.1993510
---------- MLA ----------
De La Matta, M., Lafaille, C., Kornblihtt, A.R. "First come, first served revisited: Factors affecting the same alternative splicing event have different effects on the relative rates of intron removal" . RNA, vol. 16, no. 5, 2010, pp. 904-912.
http://dx.doi.org/10.1261/rna.1993510
---------- VANCOUVER ----------
De La Matta, M., Lafaille, C., Kornblihtt, A.R. First come, first served revisited: Factors affecting the same alternative splicing event have different effects on the relative rates of intron removal. RNA. 2010;16(5):904-912.
http://dx.doi.org/10.1261/rna.1993510