Groupleader: Tamás Fischer

Recent studies carried out in a wide range of eukaryotic organisms indicate that more than 90% of the eukaryotic genome is transcriptionally active, and a large portion of the transcriptome consists of non-protein-coding RNA transcripts (ncRNAs or cryptic transcripts). Transcription of ncRNAs is linked to key chromosomal events such as chromatin remodeling, gene regulation and establishment of heterochromatic domains, but the function and significance of the widespread ncRNA transcription is not understood. While coding RNAs are packaged and exported from the nucleus, the majority of cryptic transcripts are recognized and quickly degraded by the RNA surveillance machinery. Defects in the recognition and degradation of cryptic transcripts or increased transcriptional activity outside of the genetically confined transcription units can lead to toxic accumulation of these transcripts and cause genomic instability and chromosome segregation defects.

The major goals of the research in our laboratory are:

i) to identify the epigenetic mechanisms responsible for accurate definition of transcription units and their transcripts, and to understand how these mechanisms are involved in controlling ncRNA transcription

ii) to understand how epigenetic processes control genomic stability and chromosome segregation

Our methodology includes traditional genetic, molecular biology and biochemical techniques combined with modern genomic methods, including high-throughput sequencing, tiling arrays and bioinformatics tools. We are using various yeast and mammalian cell culture systems as models.

Accumulating evidence suggests that RNA plays a much more significant role in nuclear processes than previously imagined. These studies will significantly increase our general understanding of genome organization and transcriptional regulation, and the biological significance of the recently described variety of ncRNAs in the eukaryotic cell. Mutations leading to genomic instability are a major cause of cancer development and contribute to an enhanced mutation rate in cancer cells. Increased understanding of the molecular mechanisms behind these processes will advance the development of preventive and corrective treatments for malignant cancers.