Characterization of post-transcriptional regulation of gene expression in heart diseases

• Applicant: Dr. Kemal Marc Akat
• Subject Area: Cardiology, Angiology
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 155547566

Messenger RNA-binding proteins (mRBPs) regulating alternative splicing and microRNAs, a family of non-coding RNAs of about 22 nucleotides in length, are important components of posttranscriptional gene regulation in the heart. An alteration in their function leads to arrhythmias, cardiomyopathies or cardiac hypertrophy. Examples are mRBPs of the CELF and MBNL family and the microRNAs miR-1 and miR-208. A thorough knowledge of their cell specific function is necessary for a better understanding of their role in cardiac diseases and will aid in the development of new therapies. MRBPs and microRNAs recognize their mRNA targets by binding to short nucleotide sequences, e.g. CUG or CCUG for some mRPBs and the 5‘ proximal “seed” region (the first 6 to 8 nucleotides) in the case of microRNAs. The understanding of their biological function has been limited by difficulties to reliably identify mRNA targets. Using a modified cross-linking and immunoprecipitation protocol in addition to deep sequencing methods this project aims to identify mRNA-targets of cardiac mRBPs and microRNAs and aims to characterize their RNA-binding motifs on a transcriptome wide level. The association of their genomic sequence variation and their expression in normal and diseased cardiac tissue will be investigated in a number of cardiac diseases.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Thomas Tuschl