Structured RNAs in the ENCODE selected regions of the human genome

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., Snyder, M., Gerstein, M. B., Reymond, A., Hofacker, I. L., Stadler, P. F. (2007) Structured RNAs in the ENCODE selected regions of the human genome. Genome Research, 17 (6). pp. 852-864. ISSN 10889051 (ISSN) (Public Dataset)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/17568003
DOI: 10.1101/gr.5650707

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 ∼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 ∼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%). ©2007 by Cold Spring Harbor Laboratory Press.

Item Type: Paper
Additional Information:
Uncontrolled Keywords: article comparative study controlled study DNA microarray GC rich sequence gene sequence genetic algorithm genetic conservation genetic selection genetic trait genome human nonhuman nucleotide sequence phylogeny prediction priority journal RNA structure stochastic model 3' Untranslated Regions Base Sequence Genome, Human Humans Molecular Sequence Data Quantitative Trait Loci Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger RNA, Untranslated Transcription, Genetic
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA expression
bioinformatics > computational biology
CSHL Authors:
Communities: CSHL labs > Gingeras lab
Depositing User: CSHL Librarian
Date: 2007
Date Deposited: 08 Mar 2012 16:36
Last Modified: 12 Jul 2013 20:10
PMCID: PMC1891344
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Dataset ID:
URI: http://repository.cshl.edu/id/eprint/25323

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