TILING_MICRORNA · Exploring the dark matter of the human genome: systematic discovery of microRNA genes using high-density oligonucleotide tiling arrays and comparative genome analysis

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Project objective

Protein-coding sequences represent only a tiny fraction of the human genome. Since biologists have started to explore the puzzling remainder, the 'dark matter' of the genome, the number of known non-protein-coding genes has been growing rapidly. In particular hundreds of genes encoding microRNAs (miRNAs), regulators of key molecular processes in animals and plants, have been identified over the last five years and recent studies indicate considerably higher gene numbers. As non-coding RNA genes are often less evolutionarily conserved than protein-coding genes, and mature miRNAs are hard to clone, novel sensitive approaches are required for their identification. We propose an interdisciplinary approach for discovering RNAs that combines high-throughput functional genomics, nucleotide sequence analysis, and comparative genomics. In particular, we intend to utilise a series of high-density oligonucleotide tiling arrays, which enable the sensitive measurement of transcription on the entire non-repetitive sequence (sense and antisense strands) of the human genome at high (<40 nucleotide) resolution. The approach will cover the following steps:(1) detection of transcribed genomic regions;(2) identification of regions unlikely to encode proteins;(3) detection of evolutionarily conserved blocks of DNA;(4) examination of such regions for typical properties characterising known non-coding RNA genes, e.g. stem-loop-forming potential and specific patterns of conservation.The project will involve a tight collaboration between the host laboratory and the experimental group of Michael Snyder at Yale, both experts in constructing and analysing tiling arrays. As tiling arrays allow an unbiased search for biologically relevant regions, are sensitive, and can be readily applied to distinct cell types, we expect that many novel non-coding RNA genes, including miRNA genes, will be detected. Furthermore, previously predicted gene structures will be confirmed, and refined.

Original text from CORDIS.

Participants

• EUROPEAN MOLECULAR BIOLOGY LABORATOY (EMBL) HEIDELBERG · HEIDELBERGCoordinatorGermany
• YALE UNIVERSITY · NEW HAVENUnited States

Links

• View on CORDIS