Experimental RNomics

Our group works on the identification of regulatory non-coding RNAs (ncRNAs) in various model organisms for which we have coined the term “Experimental RNomics". In particular, we are interested in the identification of ncRNAs regulating neuronal development and in the identification of ncRNAs which are involved in CNS diseases. To that end, we have characterized the entire small ncRNA transcriptome, invoIved in the differentiation of mouse ES cells into neural cells, by generating three specialized ribonucleo-protein particle (RNP)-derived cDNA libraries, i. e. from pluripotent ES cells, neural progenitors (NP) and differentiated neural cells (N/G), respectively. By high-throughput sequencing and transcriptional profiling we identified several novel miRNAs to be involved in ES cell differentiation, as well as seven small nucleolar RNAs. About half of ncRNA sequences from the three cDNA libraries mapped to intergenic or intragenic regions, designated as interRNAs and intraRNAs, respectively. Thereby, novel ncRNA candidates exhibited a predominant size of 18-30 nt, thus resembling miRNA species, but, with few exceptions, lacking canonical miRNA features. In total, about 1000 novel ncRNAs have been identified by our approach.

Based on these findings, we have generated a custom micrarray chip, covering a) novel ncRNAs from ES cell differentiation, b) ncRNAs from whole mouse brain and c) ncRNAs from dorsal root ganglia as a model system for developing neurons. We are currently applying the microarray chip to investigate differential expression of ncRNAs in mouse models of Alzheimer and Parkinsons diseases as well as within behavioural paradigms such as fear memory extinction and depression.

 

Major achievements

  •  Coordination GEN-AU Programme: ncRNAs: from identification to functional characterization
  • Member of the 7th framework EU: SysKid
  • PhD programme participant: SPIN: signal processing in neurons

 

Future Goals

  • Identification of the biological functions of neuronal ncRNAs
  • Analysis and investigation of regulatory ncRNA networks by bioinformatical methods

 

International Collaborators

Joerg Vogel, MPI, Berlin, Germany; Ralph Bock, MPI Potsdam, Germany; Jürgen Brosius, University of Münster, Germany; Yuuchi Soeno, Nippon University, Tokyo, Japan

 

Figure: The 100 most differentially expressed novel neuronal ncRNAs during ES cell differentiation. Fold changes are depicted in a log2 scale. The dendrogram to the right indicates the Euclidean distance of the expression values.