Open AccessSpecific Role of the SR Protein Splicing Factor B52 in Cell Cycle Control in Drosophila
Author(s) -
Vanya I. Rasheva,
David Knight,
Przemysław Bożko,
Katherine A. Marsh,
Maxim V. Frolov
Publication year - 2006
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.26.9.3468-3477.2006
Subject(s) - biology , rna splicing , repressor , e2f , splicing factor , sr protein , microbiology and biotechnology , transcription factor , nuclear protein , gene , genetics , rna
E2F and retinoblastoma tumor suppressor protein pRB are important regulators of cell proliferation; however, the regulation of these proteins in vivo is not well understood. InDrosophila there are two E2F genes, an activator,de2f1 , and a repressor,de2f2 . The loss ofde2f1 gives rise to the G1 /S block accompanied by the repression of E2F-dependent transcription. These defects can be suppressed by mutation ofde2f2 . In this work, we show that thede2f1 mutant phenotype is rescued by the loss of the pre-mRNA splicing factor SR protein B52. Mutations inB52 restore S phase in clones ofde2f1 mutant cells and phenocopy the loss of thede2f2 function.B52 acts upstream ofde2f2 and plays a specific role in regulation ofde2f2 pre-mRNA splicing. In B52-deficient cells, the level of dE2F2 protein is severely reduced and the expression of dE2F2-dependent genes is deregulated. Reexpression of the intronless copy of dE2F2 in B52-deficient cells restores the dE2F2-mediated repression. These results uncover a previously unrecognized role of the splicing factor in maintaining the G1 /S block in vivo by specific regulation of the dE2F2 repressor function.