Identification and classification of conserved RNA secondary structures in the human genome.
The discoveries of microRNAs and riboswitches, among others, have shown functional RNAs to be biologically more important and genomically more prevalent than previously anticipated. We have developed a general comparative genomics method based on phylogenetic stochastic context-free grammars for identifying functional RNAs encoded in the human genome and used it to survey an eight-way genome-wide alignment of the human, chimpanzee, mouse, rat, dog, chicken, zebra-fish, and puffer-fish genomes for deeply conserved functional RNAs. At a loose threshold for acceptance, this search resulted in a set of 48,479 candidate RNA structures. This screen finds a large number of known functional RNAs, including 195 miRNAs, 62 histone 3'UTR stem loops, and various types of known genetic recoding elements. Among the highest-scoring new predictions are 169 new miRNA candidates, as well as new candidate selenocysteine insertion sites, RNA editing hairpins, RNAs involved in transcript auto regulation, and many folds that form singletons or small functional RNA families of completely unknown function. While the rate of false positives in the overall set is difficult to estimate and is likely to be substantial, the results nevertheless provide evidence for many new human functional RNAs and present specific predictions to facilitate their further characterization.
Pedersen
Jakob Skou
JS
Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, California, USA. jsp@soe.ucsc.edu
Bejerano
Gill
G
Siepel
Adam
A
Rosenbloom
Kate
K
Lindblad-Toh
Kerstin
K
Lander
Eric S
ES
Kent
Jim
J
Miller
Webb
W
Haussler
David
D
D020413:3' Untranslated Regions; D000818:Animals; D002645:Chickens; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D004285:Dogs; D016678:Genome; D015894:Genome, Human; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D051381:Rats; D017423:Sequence Analysis, RNA / Q000379:methods*; D023721:Tetraodontiformes; D015027:Zebrafish
D020413:3' Untranslated Regions; D035683:MicroRNAs