Comparative genomics reveals unusually long motifs in mammalian genomes.
BACKGROUND
The recent discovery of the first small modulatory RNA (smRNA) presents the challenge of finding other molecules of similar length and conservation level. Unlike short interfering RNA (siRNA) and micro-RNA (miRNA), effective computational and experimental screening methods are not currently known for this species of RNA molecule, and the discovery of the one known example was partly fortuitous because it happened to be complementary to a well-studied DNA binding motif (the Neuron Restrictive Silencer Element).


RESULTS
The existing comparative genomics approaches (e.g., phylogenetic footprinting) rely on alignments of orthologous regions across multiple genomes. This approach, while extremely valuable, is not suitable for finding motifs with highly diverged "non-alignable" flanking regions. Here we show that several unusually long and well conserved motifs can be discovered de novo through a comparative genomics approach that does not require an alignment of orthologous upstream regions. These motifs, including Neuron Restrictive Silencer Element, were missed in recent comparative genomics studies that rely on phylogenetic footprinting. While the functions of these motifs remain unknown, we argue that some may represent biologically important sites.


BACKGROUND
Our comparative genomics software, a web-accessible database of our results and a compilation of experimentally validated binding sites for NRSE can be found at http://www.cse.ucsd.edu/groups/bioinformatics.
Jones
Neil C
NC
Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.
Pevzner
Pavel A
PA
D000465:Algorithms; D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D002874:Chromosome Mapping / Q000379:methods*; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics*; D000099229:RE1-Silencing Transcription Factor
D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor