RNA polymerase II C-terminal domain mediates regulation of alternative splicing by SRp20

DE LA MATA, M; KORNBLIHTT, A

NATURE STRUCTURAL & MOLECULAR BIOLOGY

NATURE PUBLISHING GROUP

Año: 2006 vol. 13 p. 973 - 980

1545-9985

Previous studies have linked the carboxy terminal domain (CTD) of RNA polymerase II (pol II) with co-transcriptional pre-mRNA processing, but little is known about the CTD function in alternative splicing (AS). In this work we have used the α-amanitin resistant pol II system and fibronectin 1 minigenes to study the role of the CTD in the regulation of splice site selection. Although no direct physical interaction has been described between pol II CTD and SR proteins, we found that the CTD is required for SRp20 inhibitory action on FN EDI exon inclusion, whereas SF2/ASF stimulating effect is CTD-independent. CTD phosphorylation controls transcription elongation and is a major contributor to AS regulation. However, the SRp20 effect is still observed when transcription elongation is reduced. Together these results suggest that the CTD acts by recruiting SRp20 to the EDI alternative exon leading to exon skipping and that elongation and factor recruitment contribute independently to the transcriptional control of alternative splicing.