GEN-AU Non-coding RNAs - From identification to functional characterization

In cells from all organisms studied to date two different types of RNAs are found: messenger RNAs (mRNAs), which are translated into proteins and so-called non-protein-coding RNAs (ncRNAs), which are not translated into proteins but function at the level of the RNA itself. Many known ncRNAs, such as miRNAs, are involved in the regulation of gene expression. Presently, the annotation of ncRNAs in the genomes of various organisms has been a difficult task for bioinformatics and experimental approaches (e. g. by the generation of cDNA libraries encoding ncRNAs). Thus, in the human genome the predictions on the number of ncRNA genes range from about 1.000 up to 400.000 (estimated from tiling-array experiments). In comparison, about 20.000 human protein-coding genes are being estimated. These findings raise two important questions to the ncRNA field: 1) how many of these ncRNAs really exist in genomes of model organisms and 2) what are their functions? Both questions are intimately connected, because it is expected that novel ncRNAs might fulfill functions that expand the known repertoire of RNA (e.g. induction of heterochromatin formation). Only if the function of a RNA can be elucidated, this RNA species will be assigned as a bona fide ncRNA (otherwise, the RNA might represent a spurious transcript or degradation product without any function). Hence, the proposed application termed: Non-coding RNAs: from identification to functional characterization deals with these two major questions in genomic research. By employing sophisticated selection procedures for experimentally identifying novel ncRNAs in various genomes, we subsequently aim to reveal their cellular role(s). At the same time, we will elucidate the biological function of some known ncRNAs (specifically miRNAs and riboswitch RNAs) as crucial genetic switches in the regulation of gene expression. In addition, we will study the roles of selected miRNAs in neuronal differentiation and in human diseases, such as obesity, atherosclerosis and neuro-degeneration. The experimental data will be complemented and validated by bioinformatical prediction as well as classifications of ncRNAs, employing novel computational algorithms. Both, experimental and computational approaches will enable a better understanding of gene regulation, gene function and involvement of ncRNAs in human diseases. Subproject 9: Functional characterization of microRNA-mRNA pairs targeting adipogenesis and obesity