Bioinformatics Centre > Research > microRNA

microRNAs

The microRNA group at the Bioinformatics Centre conducts research into the biology of microRNAs using computational methods.Together with the promotor group, we are part of an effort sponsored by the Novo Nordisk Foundation to analyse and predict the regulation of gene expression.We analyse the biology of microRNAs using computational methods and develop tools useful by experimental biologists. It is the connection between computational tasks and biological knowledge that we find especially intriguing.

The role of microRNAs in gene regulatory networks

We are witnessing a shift in our understanding of the complexityin gene regulatory networks caused by the discovery of microRNAs (miRNAs). miRNAs are a large class of non-coding 22 nucleotide RNAs,first discovered in Caenorhabditis elegans more than a decade ago,which regulate gene expression at the post-transcriptional level. Thisis achieved through base-pairing with the 3’UTR of the target gene,causing cleavage of the cognate mRNA(in plants) or, preventingtranslation initiation and/or causing target mRNA degradation(inanimals). To understand the effect of individual microRNAs on thephenotype, it still remains to place miRNAs in the overall network ofgene regulation and to discover the system level role of miRNAs on geneexpression and consequently phenotype.

One important and very succesful approach to unravel thephenotypic role of individual microRNAs is detailed experimentalstudies in various model systems. However, the problem can also beapproached from a computational angle, which is what we want to do.

Many kinds of information are important to shed light on miRNAfunctions, but in isolation each information modality is often toolimited to be useful. Therefore, we want to integrate or synthesiseseveral information sources to build tools capable of generatingtestable hypothesis about the role of individual microRNAs.

The following is a non-exhaustive list of information sources we are working to integrate.

• Genes targeted by microRNAs. Some experimentally confirmed, many more predicted by existing algorithms combined with phylogenetic footprinting. Provides physical interaction links between microRNAs and proteins.
• Expression information. There are already very large amounts of public domain information about the expression of microRNAs. This provides tissue expression profiles for miRNAs, as well as links between miRNAs that share the same expression pattern. Many groups are planning to systematically perturb different model systems and measure both mRNA and miRNA expression. (We have connections to some of these groups). Such information enables us to determine the covariation between microRNA and protein expression, indicating a regulatory relationship between a protein and a mRNA(can be indirect and can the protein regulating the miRNA or vice versa)

• Intracellular network data. Several public databases (such as KEGG) provide reasonably reliable data about intracellular networks. Identifying and mapping relevant microRNA interactions onto these networks, has the potential to improve both the understanding of the pathways as well the function of the microRNAs.
• Transcriptional regulation. Regulation of transcription is central to the understanding of gene expression. This project will integrate with the efforts of a large team at the bioinformatics centre focusing on transcriptional regulation. Identification of the transcription factors that regulate miRNAs provides links from transcription factors to miRNAs.

Selected publications

Lindow M and Krogh A, Computational evidence for hundreds of non-conserved plant microRNAs, BMC Genomics 2005, 6:119

Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH, Programmed cell death 4 (PDCD4) is an importantfunctional target of the microRNA miR-21 in breast cancer cells. J Biol Chem (2007)

Lindow M, Jacobsen A, Nygaard S, Mang Y, Krogh A., IntragenomicMatching Reveals a Huge Potential for miRNA-Mediated Regulation inPlants. PLoS Comput Biol 3(11): e238