Searching Genomes for NonCoding RNAs:
In the last 10 years, non-coding RNAs have been found to have many functions in cells and organisms. While only 2% of eukaryotic genomes are translated, as much as 80% of may be transcribed. This suggests that there are hundreds of thousands of RNAs about which little is known. Computational methods will be needed to find these RNAs in newly sequenced genomes and to make predictions about their structure and function.
One bioinformatic challenge is that, without an open reading frame as a clue, it is difficult to find putative non-coding RNA genes in a DNA sequence. Comparing the same non-coding RNA between organisms, it is common for them to share the same secondary structure, but the primary sequence is frequently divergent. Thus, genome searching for non-coding RNA genes becomes a problem in scanning DNA sequences for regions that can fold up into a characteristic RNA secondary structure (left figure).
Our project is aimed at profiling noncoding RNA structures, and aligning RNA structures to genomes in order to find new instances of a given non-coding RNA gene family. Our methods can model the RNA structural motif of pseudoknots (right figure) as well as stem loops. RNATOPS is our genome search program.
Current projects include algorithm development, graphical user interface development, and the application of our methods to certain families of RNAs. We have recently been studying telomerase RNAs in fungal species, identifying instances in newly sequenced genomes with the aide of a special computational tool, TRFolder, which can predict many of the unique structural features of telomerase RNAs, including the conserved pseudoknot with triple helix. RNApasta is a multiple structural alignment analysis and editor program with a graphicaluser interface.
Evolution of RNA Structure:
We have also been studying the evolution of RNA structure in certain bacterial RNA families with the goal of describing the patterns of sequence and base-pair changes. that underlie the gain and loss of RNA structural motifs (stems, pseudoknots) across phylogenies. The figure shows changes in the length of a given stem mapped on to an organismal phylogenetic tree.
Please visit our RNA-Informatics web site.