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Ye Ding, Ph.D.
With the discovery of RNA interference (RNAi), microRNAs, and riboswitches, RNAs are more important than previously thought for their versatile regulatory functions. In 2002, small RNAs were named the number one breakthrough of the year by Science.
The long term objectives of our RNA Bioinformatics program are:
- Developing efficient and improved algorithms for RNA higher order structure prediction;
- Developing computational tools for RNA structured-based applications;
- Making these tools available to the scientific community through software and web server;
- Applying these tools to molecular biology problems of high scientific significance through collaborations with molecular biologists.
RNA-targeting nucleic acids including antisense oligonucleotides, trans-cleaving ribozymes and short interfering RNAs (siRNAs) are important tools for achieving efficient gene down-regulation. They are essential for functional studies of genes and gene products in humans, model organisms and infectious pathogens, as well as for the identification and validation of new therapeutic targets and agents against human diseases. To be effective, these antisense nucleic acid molecules require good target accessibility, which is primarily determined by the secondary structure of the target RNA. The secondary structures of mRNAs and viral RNAs are generally unknown, and are difficult to elucidate by experimental means. Therefore, computational methods could be valuable for the RNA structural determination.
We have developed a novel algorithm suitable for this purpose. It is conservatively estimated that there are at least 800 human microRNAs, and over 30% of human genes are microRNA targets. MicroRNAs are also reported to be associated with human cancers. In human genome, over 60% of pre-mRNAs are alternatively spliced, and yet the underlying mechanism is poorly understood. The current applications focus on the development of Bioinformatics tools for the rational design of RNA-targeting nucleic acids, and the identification of microRNA targets. Also of high interest is gene regulation by small bacterial RNAs (sRNAs), another class of non-coding RNAs (ncRNAs), and structural basis of eukaryotic splicing.