Structured RNAs in the ENCODE selected regions of the human genome.

Stefan Washietl; Jakob Skou Pedersen; Jan O Korbel; Claudia Stocsits; Andreas R Gruber; Jörg Hackermüller; Jana Hertel; Manja Lindemeyer; Kristin Reiche; Andrea Tanzer; Catherine Ucla; Carine Wyss; Stylianos E Antonarakis; France Denoeud; Julien Lagarde; Jorg Drenkow; Philipp Kapranov; Thomas R Gingeras; Roderic Guigó; Michael Snyder; Mark B Gerstein; Alexandre Reymond; Ivo L Hofacker; Peter F Stadler

doi:10.1101/gr.5650707

Structured RNAs in the ENCODE selected regions of the human genome.

Stefan Washietl, Jakob Skou Pedersen, Jan O Korbel, Claudia Stocsits, Andreas R Gruber, Jörg Hackermüller, Jana Hertel, Manja Lindemeyer, Kristin Reiche, Andrea Tanzer, Catherine Ucla, Carine Wyss, Stylianos E Antonarakis, France Denoeud, Julien Lagarde, Jorg Drenkow, Philipp Kapranov, Thomas R Gingeras, Roderic Guigó, Michael SnyderMark B Gerstein, Alexandre Reymond, Ivo L Hofacker, Peter F Stadler

Functional Genomics

125 Citations (Scopus)

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%).

Original language	English
Journal	Genome Research
Volume	17
Issue number	6
Pages (from-to)	852-64
Number of pages	12
ISSN	1088-9051
DOIs	https://doi.org/10.1101/gr.5650707
Publication status	Published - 2007

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Washietl, S., Pedersen, J. S., Korbel, J. O., Stocsits, C., Gruber, A. R., Hackermüller, J., Hertel, J., Lindemeyer, M., Reiche, K., Tanzer, A., Ucla, C., Wyss, C., Antonarakis, S. E., Denoeud, F., Lagarde, J., Drenkow, J., Kapranov, P., Gingeras, T. R., Guigó, R., ... Stadler, P. F. (2007). Structured RNAs in the ENCODE selected regions of the human genome. Genome Research, 17(6), 852-64. https://doi.org/10.1101/gr.5650707

Washietl, S, Pedersen, JS, Korbel, JO, Stocsits, C, Gruber, AR, Hackermüller, J, Hertel, J, Lindemeyer, M, Reiche, K, Tanzer, A, Ucla, C, Wyss, C, Antonarakis, SE, Denoeud, F, Lagarde, J, Drenkow, J, Kapranov, P, Gingeras, TR, Guigó, R, Snyder, M, Gerstein, MB, Reymond, A, Hofacker, IL & Stadler, PF 2007, 'Structured RNAs in the ENCODE selected regions of the human genome.', Genome Research, vol. 17, no. 6, pp. 852-64. https://doi.org/10.1101/gr.5650707

@article{c9fe2df04dc411dd8d9f000ea68e967b,

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%).",

author = "Stefan Washietl and Pedersen, {Jakob Skou} and Korbel, {Jan O} and Claudia Stocsits and Gruber, {Andreas R} and J{\"o}rg Hackerm{\"u}ller and Jana Hertel and Manja Lindemeyer and Kristin Reiche and Andrea Tanzer and Catherine Ucla and Carine Wyss and Antonarakis, {Stylianos E} and France Denoeud and Julien Lagarde and Jorg Drenkow and Philipp Kapranov and Gingeras, {Thomas R} and Roderic Guig{\'o} and Michael Snyder and Gerstein, {Mark B} and Alexandre Reymond and Hofacker, {Ivo L} and Stadler, {Peter F}",

note = "Keywords: 3' Untranslated Regions; Base Sequence; GC Rich Sequence; Genome, Human; Humans; Molecular Sequence Data; Quantitative Trait Loci; RNA, Messenger; RNA, Untranslated; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic",

year = "2007",

doi = "10.1101/gr.5650707",

language = "English",

volume = "17",

pages = "852--64",

journal = "Genome Research",

issn = "1088-9051",

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TY - JOUR

T1 - Structured RNAs in the ENCODE selected regions of the human genome.

AU - Washietl, Stefan

AU - Pedersen, Jakob Skou

AU - Korbel, Jan O

AU - Stocsits, Claudia

AU - Gruber, Andreas R

AU - Hackermüller, Jörg

AU - Hertel, Jana

AU - Lindemeyer, Manja

AU - Reiche, Kristin

AU - Tanzer, Andrea

AU - Ucla, Catherine

AU - Wyss, Carine

AU - Antonarakis, Stylianos E

AU - Denoeud, France

AU - Lagarde, Julien

AU - Drenkow, Jorg

AU - Kapranov, Philipp

AU - Gingeras, Thomas R

AU - Guigó, Roderic

AU - Snyder, Michael

AU - Gerstein, Mark B

AU - Reymond, Alexandre

AU - Hofacker, Ivo L

AU - Stadler, Peter F

N1 - Keywords: 3' Untranslated Regions; Base Sequence; GC Rich Sequence; Genome, Human; Humans; Molecular Sequence Data; Quantitative Trait Loci; RNA, Messenger; RNA, Untranslated; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic

PY - 2007

Y1 - 2007

N2 - 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%).

AB - 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%).

U2 - 10.1101/gr.5650707

DO - 10.1101/gr.5650707

M3 - Journal article

C2 - 17568003

SN - 1088-9051

VL - 17

SP - 852

EP - 864

JO - Genome Research

JF - Genome Research

IS - 6

ER -

Structured RNAs in the ENCODE selected regions of the human genome.

Abstract

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