Altered serine/arginine-rich protein phosphorylation and exonic enhancer-dependent splicing in Mammalian cells lacking topoisomerase I - Archive ouverte HAL
Journal Articles Cancer Research Year : 2003

Altered serine/arginine-rich protein phosphorylation and exonic enhancer-dependent splicing in Mammalian cells lacking topoisomerase I

M. Gabut
C. Dupon
  • Function : Author
G. Kohlhagen
  • Function : Author
Y. Pommier
  • Function : Author

Abstract

DNA topoisomerase I (Topo I) specifically phosphorylates arginine-serine-rich (SR proteins) splicing factors and is potentially involved in pre-mRNA-splicing regulation. Using a Topo I-deficient murine B lymphoma-derived subclone (P388-45/C) selected for its resistance to high dosage of the antitumor drug camptothecin, we show that Topo I depletion results in the hypophosphorylation of SR proteins and impairs exonic splicing enhancer (ESE)-dependent but not constitutive splicing. The Affymetrix GeneChip system analysis revealed that several alternatively spliced genes, characterized by small exons and large introns, are down-regulated in Topo I-deficient cells. Given that ectopic expression of green fluorescent protein-Topo I fusion in Topo I-deficient cells restores both wild-type phosphorylation of SR proteins and ESE-dependent splicing, we conclude that Topo I-mediated phosphorylation plays a specific role in ESE-regulated splicing.
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Dates and versions

hal-02199832 , version 1 (31-07-2019)

Identifiers

  • HAL Id : hal-02199832 , version 1

Cite

M. Gabut, C. Dupon, G. Kohlhagen, J. Stevenin, Y. Pommier, et al.. Altered serine/arginine-rich protein phosphorylation and exonic enhancer-dependent splicing in Mammalian cells lacking topoisomerase I. Cancer Research, 2003, 63 (23), pp.8203--11. ⟨hal-02199832⟩
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