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