Structured RNAs in the ENCODE selected regions of the human genome.
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%).
Washietl
Stefan
S
Institute for Theoretical Chemistry, University of Vienna, A-1090 Wien, Austria. wash@tbi.univie.ac.at
Pedersen
Jakob S
JS
Korbel
Jan O
JO
Stocsits
Claudia
C
Gruber
Andreas R
AR
Hackermüller
Jörg
J
Hertel
Jana
J
Lindemeyer
Manja
M
Reiche
Kristin
K
Tanzer
Andrea
A
Ucla
Catherine
C
Wyss
Carine
C
Antonarakis
Stylianos E
SE
Denoeud
France
F
Lagarde
Julien
J
Drenkow
Jorg
J
Kapranov
Philipp
P
Gingeras
Thomas R
TR
Guigó
Roderic
R
Snyder
Michael
M
Gerstein
Mark B
MB
Reymond
Alexandre
A
Hofacker
Ivo L
IL
Stadler
Peter F
PF
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
D020413:3' Untranslated Regions; D012333:RNA, Messenger; D022661:RNA, Untranslated