title: Structured RNAs in the ENCODE selected regions of the human genome.
abstract: Functional RNA structures play an important role both in the context of noncoding RNA transcripts as well as regulatory elements in mRNAs. Here we present a computational study to detect functional RNA structures within the ENCODE regions of the human genome. Since structural RNAs in general lack characteristic signals in primary sequence, comparative approaches evaluating evolutionary conservation of structures are most promising. We have used three recently introduced programs based on either phylogenetic-stochastic context-free grammar (EvoFold) or energy directed folding (RNAz and AlifoldZ), yielding several thousand candidate structures (corresponding to approximately 2.7% of the ENCODE regions). EvoFold has its highest sensitivity in highly conserved and relatively AU-rich regions, while RNAz favors slightly GC-rich regions, resulting in a relatively small overlap between methods. Comparison with the GENCODE annotation points to functional RNAs in all genomic contexts, with a slightly increased density in 3'-UTRs. While we estimate a significant false discovery rate of approximately 50%-70% many of the predictions can be further substantiated by additional criteria: 248 loci are predicted by both RNAz and EvoFold, and an additional 239 RNAz or EvoFold predictions are supported by the (more stringent) AlifoldZ algorithm. Five hundred seventy RNAz structure predictions fall into regions that show signs of selection pressure also on the sequence level (i.e., conserved elements). More than 700 predictions overlap with noncoding transcripts detected by oligonucleotide tiling arrays. One hundred seventy-five selected candidates were tested by RT-PCR in six tissues, and expression could be verified in 43 cases (24.6%).
authors.affiliation: Institute for Theoretical Chemistry, University of Vienna, A-1090 Wien, Austria. wash@tbi.univie.ac.at
authors.forename: Stefan
authors.initials: S
authors.lastname: Washietl
authors.forename: Jakob S
authors.initials: JS
authors.lastname: Pedersen
authors.forename: Jan O
authors.initials: JO
authors.lastname: Korbel
authors.forename: Claudia
authors.initials: C
authors.lastname: Stocsits
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Gruber
authors.forename: Jörg
authors.initials: J
authors.lastname: Hackermüller
authors.forename: Jana
authors.initials: J
authors.lastname: Hertel
authors.forename: Manja
authors.initials: M
authors.lastname: Lindemeyer
authors.forename: Kristin
authors.initials: K
authors.lastname: Reiche
authors.forename: Andrea
authors.initials: A
authors.lastname: Tanzer
authors.forename: Catherine
authors.initials: C
authors.lastname: Ucla
authors.forename: Carine
authors.initials: C
authors.lastname: Wyss
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: France
authors.initials: F
authors.lastname: Denoeud
authors.forename: Julien
authors.initials: J
authors.lastname: Lagarde
authors.forename: Jorg
authors.initials: J
authors.lastname: Drenkow
authors.forename: Philipp
authors.initials: P
authors.lastname: Kapranov
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Gingeras
authors.forename: Roderic
authors.initials: R
authors.lastname: Guigó
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Mark B
authors.initials: MB
authors.lastname: Gerstein
authors.forename: Alexandre
authors.initials: A
authors.lastname: Reymond
authors.forename: Ivo L
authors.initials: IL
authors.lastname: Hofacker
authors.forename: Peter F
authors.initials: PF
authors.lastname: Stadler
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D020862:GC Rich Sequence; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D012333:RNA, Messenger; D022661:RNA, Untranslated