IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
artículos
Título:
First come, first served revisited: factors affecting the same alternative splicing event have different effects on the relative rates of intron removal.
Autor/es:
DE LA MATA, M; LAFAILLE C; KORNBLIHTT AR
Revista:
RNA (NEW YORK, N.Y.)
Editorial:
COLD SPRING HARBOR LAB PRESS
Referencias:
Año: 2010 p. 905 - 912
ISSN:
1355-8382
Resumen:
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.