tailieunhanh - Báo cáo khóa học: A multi-protein complex containing cold shock domain (Y-box) and polypyrimidine tract binding proteins forms on the vascular endothelial growth factor mRNA Potential role in mRNA stabilization

Vascular endothelial growth factor (VEGF) is a key regu-lator of angiogenesis and post-transcriptional regulation plays a major role in VEGF expression. Both the 5¢-and 3¢-UTR are required for VEGF post-transcriptional regu-lation but factors binding to functional sequences within the 5¢-UTR have not been fully characterized. We report here the identification of complexes, binding to theVEGF mRNA 5¢-and3¢-UTR, that contain cold shock domain (CSD) and polypyrimidine tract binding (PTB) RNA binding proteins. . | Eur. J. Biochem. 271 648-660 2004 FEBS 2004 doi A multi-protein complex containing cold shock domain Y-box and polypyrimidine tract binding proteins forms on the vascular endothelial growth factor mRNA Potential role in mRNA stabilization Leeanne S. Coles1 M. Antonetta Bartlev1 Andrew Bert1 Julie Hunter1 Steven Polvak2 Peter Diamond1 . Mathew A. Vadas1 3 and Gregory J. Goodall1 3 1 Division of Human Immunology The Hanson Institute Institute of Medical and Veterinary Science 2Division of Biochemistry Department of Molecular Biosciences The University of Adelaide 3Department of Medicine The University of Adelaide North Terrace Adelaide South Australia Australia Vascular endothelial growth factor VEGF is a key regulator of angiogenesis and post-transcriptional regulation plays a major role in VEGF expression. Both the 5 - and 3 -UTR are required for VEGF post-transcriptional regulation but factors binding to functional sequences within the 5 -UTR have not been fully characterized. We report here the identification of complexes binding to the VEGF mRNA 5 - and 3 -UTR that contain cold shock domain CSD and polypyrimidine tract binding PTB RNA binding proteins. Analysis of the CSD PTB binding sites revealed a potential role in VEGF mRNA stability in both noninduced and induced conditions demonstrating a general stabilizing function. Such a stabilizing mechanism had not been reported previously for the VEGF gene. We further found that the CSD PTB-containing complexes are large multiprotein complexes that are most likely preformed in solution and we demonstrate that PTB is associated with the VEGF mRNA in vivo. Complex lormaiion between CSD proteins and PTB has not been reported previously. Analysis of the CSD PTB RNA binding sites revealed a novel CSD protein RNA recognition site and also demonstrated that CSD proteins may direct the binding of CSD PTB complexes. We found the same complexes binding to an RNA-stabilizing element of another