The role of long, non-protein coding RNAs (lncRNAs) in gene and genome regulation

The genome encodes all the information required to direct the development of an organism from the fertilized egg into a complex human organism. Mis-regulation in these gene programs can lead to cancer, in children and adults. A novel class of genes, the long, non-protein coding RNAs (lncRNAs) and their role in gene and genome regulation are receiving increased attention as potential therapeutic targets to control gene and genome activity and reverse such mis-regulated gene programs.

LncRNA genes produce RNA molecules as any protein coding gene, but the RNA is not getting translated into larger peptides or proteins. Instead, either the RNA itself serves a biomolecule and interacts with other components in a cell such as DNA, RNA or proteins, or the process of generating the RNA itself already is functional with respect to gene and genome activity. While initially such lncRNA genes were disregarded as noise, in recent years several labs around the world could show that lncRNA genes actually can have important functions for the organism. In addition, deep profiling of all RNA species in cells and tissues by next generation sequencing, led to discovery that almost as many lncRNA genes are embedded in the human genome as protein coding genes. This led to fascinating research in how such lncRNA genes can actually exert their function and how novel anti-sense based drug approaches can amend their function for a beneficially outcome in various genetic diseases.

Function of lncRNAs in oncology

Our research pioneered the genetic analysis of lncRNA function in a whole organism context. We discovered that the two lncRNA genes Fendrr and Handsdown are essential for the organism and in particular for regulating specific gene programs. While our genetic approach defined that Fendrr acts on the RNA level, we show that the Handsdown lncRNA locus exerts its function via its transcription. We are focused previously at developmental gene programs in the cardiac system and are expanding our research, towards the role of lncRNAs in oncology. In particular the gene programs regulated by the above mentioned two lncRNA genes are also involved in small lung cell cancer and endometrial cancer, respectively.

We are using mouse models to understand the function of lncRNAs in an organismal and disease context, thereby understanding more about genome regulation by lncRNAs and exploring potential drug targets for intervention.