Regulation of mammalian mRNA splicing by CA repeat enhancer elements

• Applicant: Professor Dr. Albrecht Bindereif
• Subject Area: Cell Biology
• Term: from 2001 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5468076

Mammalian mRNA splicing is often regulated through RNA splicing enhancers that influence splicing efficiency and the use of alternative splice sites. Splicing enhancers usually reside in exons, often consist of purine- or CA-rich sequences, and function through binding of regulatory protein factors. This project focuses on the human gene for endothelial nitric oxide synthase (e-NOS), which plays a key role in vascular homeostasis and has been implicated as a determinant of atherosclerosis and cardiovascular diseases. There is a polymorphic CA repeat region in intron 13, for which a correlation between the number of CA repeats and the risk for coronary artery disease has been recently discovered. In preliminary work we have identified this CA repeat region in intron 13 as an unusual splicing enhancer element, the activity of which depends on the CA repeat number. Specific aims of this project are to characterize the mechanism of action of the CA repeat region as a splicing-regulatory element, including its interactions with proteins and the general splicing machinery, and to assess its functional significance in alternative splicing. In addition, these findings will be extended to other CA repeat-containing human genes.

• DFG Programme: Research Units
• Subproject of: FOR 426: Complex RNA-protein interactions in the maturation and function of eukaryotic mRNA
• Major Instrumentation: PCR Analyse-System
• Instrumentation Group: 1150 Thermocycler (PCR)