BimL upregulation induced by BCR cross-linking in BL41 Burkitt's lymphoma results from a splicing mechanism of the BimEL mRNA.
B lymphocyte receptor-mediated apoptosis is associated with increased expression of the BimL isoform of Bim. The mechanisms involved in the regulation of BimL protein expression are still unknown. We report that BimL expression following BCR activation is not associated with a specific increase of BimL mRNA but rather to the intron retention structure of the BimEL mRNA. Indeed, expression of a BimEL cDNA leads in Hela cells leads to the production of both BimEL and BimL proteins. Mutation of the intron-splicing GT sequence present in the exon 3 results in the production of only BimEL protein. Ectopic expression of BimEL cDNA resulted in a large increase of BimL expression upon BCR-stimulation, whereas cells transfected with the GT/AA mutated form of BimEL only produced BimEL proteins upon BCR-activation. These data showed that BimL expression induced by BCR activation may result from the splicing of BimEL mRNA independently of Bim promoter regulation.
Clybouw
Cyril
C
INSERM U., Université Paris-Sud, Hôpital Paul Brousse, Villejuif, France.
Hadji
Abbas
A
ElMchichi
Bouchra
B
Auffredou
Marie-Thérèse
MT
Leca
Gérald
G
Vazquez
Aimé
A