Nucleic Acids Research, 2001, Vol. 29, No. 10 2135-2144
© 2001 Oxford University Press
Discovering common stem–loop motifs in unaligned RNA sequences
Department of Genetics and Ecology, The Institute of Biological Sciences, University of Aarhus, Building 540, Ny Munkegade, DK-8000 Aarhus C, Denmark and 1Department of Genetics, Washington University Medical School, 660 S. Euclid, Box 8232, St Louis, MO 63110, USA
Post-transcriptional regulation of gene expression is often accomplished by proteins binding to specific sequence motifs in mRNA molecules, to affect their translation or stability. The motifs are often composed of a combination of sequence and structural constraints such that the overall structure is preserved even though much of the primary sequence is variable. While several methods exist to discover transcriptional regulatory sites in the DNA sequences of coregulated genes, the RNA motif discovery problem is much more difficult because of covariation in the positions. We describe the combined use of two approaches for RNA structure prediction, FOLDALIGN and COVE, that together can discover and model stem–loop RNA motifs in unaligned sequences, such as UTRs from post-transcriptionally coregulated genes. We evaluate the method on two datasets, one a section of rRNA genes with randomly truncated ends so that a global alignment is not possible, and the other a hyper-variable collection of IRE-like elements that were inserted into randomized UTR sequences. In both cases the combined method identified the motifs correctly, and in the rRNA example we show that it is capable of determining the structure, which includes bulge and internal loops as well as a variable length hairpin loop. Those automated results are quantitatively evaluated and found to agree closely with structures contained in curated databases, with correlation coefficients up to 0.9. A basic server, Stem–Loop Align SearcH (SLASH), which will perform stem–loop searches in unaligned RNA sequences, is available at http://www.bioinf.au.dk/slash/.
* To whom correspondence should be addressed. Tel: +1 314 747 5534; Fax: +1 314 362 7855; Email: stormo{at}genetics.wustl.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Parisien, J. A. Cruz, E. Westhof, and F. Major New metrics for comparing and assessing discrepancies between RNA 3D structures and models RNA, October 1, 2009; 15(10): 1875 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Fan, P. B. Bitterman, and O. Larsson Regulatory element identification in subsets of transcripts: Comparison and integration of current computational methods RNA, August 1, 2009; 15(8): 1469 - 1482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Smit, R. Knight, and J. Heringa RNA structure prediction from evolutionary patterns of nucleotide composition Nucleic Acids Res., April 1, 2009; 37(5): 1378 - 1386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Seemann, J. Gorodkin, and R. Backofen Unifying evolutionary and thermodynamic information for RNA folding of multiple alignments Nucleic Acids Res., November 1, 2008; 36(20): 6355 - 6362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B. Do, C.-S. Foo, and S. Batzoglou A max-margin model for efficient simultaneous alignment and folding of RNA sequences Bioinformatics, July 1, 2008; 24(13): i68 - i76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Xu, Y. Ji, and G. D. Stormo RNA Sampler: a new sampling based algorithm for common RNA secondary structure prediction and structural alignment Bioinformatics, August 1, 2007; 23(15): 1883 - 1891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Torarinsson, J. H. Havgaard, and J. Gorodkin Multiple structural alignment and clustering of RNA sequences Bioinformatics, April 15, 2007; 23(8): 926 - 932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Voss Structural analysis of aligned RNAs Nucleic Acids Res., November 14, 2006; 34(19): 5471 - 5481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Baird, M. Turcotte, R. G. Korneluk, and M. Holcik Searching for IRES RNA, October 1, 2006; 12(10): 1755 - 1785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. BINDEWALD and B. A. SHAPIRO RNA secondary structure prediction from sequence alignments using a network of k-nearest neighbor classifiers. RNA, March 1, 2006; 12(3): 342 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yao, Z. Weinberg, and W. L. Ruzzo CMfinder--a covariance model based RNA motif finding algorithm Bioinformatics, February 15, 2006; 22(4): 445 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Havgaard, R. B. Lyngso, and J. Gorodkin The FOLDALIGN web server for pairwise structural RNA alignment and mutual motif search Nucleic Acids Res., July 1, 2005; 33(suppl_2): W650 - W653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Havgaard, R. B. Lyngso, G. D. Stormo, and J. Gorodkin Pairwise local structural alignment of RNA sequences with sequence similarity less than 40% Bioinformatics, May 1, 2005; 21(9): 1815 - 1824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kawaguchi and J. Bailey-Serres mRNA sequence features that contribute to translational regulation in Arabidopsis Nucleic Acids Res., February 16, 2005; 33(3): 955 - 965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. KNIGHT, A. BIRMINGHAM, and M. YARUS BayesFold: Rational 2{degrees} folds that combine thermodynamic, covariation, and chemical data for aligned RNA sequences RNA, September 1, 2004; 10(9): 1323 - 1336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pavesi, G. Mauri, M. Stefani, and G. Pesole RNAProfile: an algorithm for finding conserved secondary structure motifs in unaligned RNA sequences Nucleic Acids Res., June 15, 2004; 32(10): 3258 - 3269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-J. Hu GPRM: a genetic programming approach to finding common RNA secondary structure elements Nucleic Acids Res., July 1, 2003; 31(13): 3446 - 3449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B. Fogel, V. W. Porto, D. G. Weekes, D. B. Fogel, R. H. Griffey, J. A. McNeil, E. Lesnik, D. J. Ecker, and R. Sampath Discovery of RNA structural elements using evolutionary computation Nucleic Acids Res., December 1, 2002; 30(23): 5310 - 5317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. V. Benos, M. L. Bulyk, and G. D. Stormo Additivity in protein-DNA interactions: how good an approximation is it? Nucleic Acids Res., October 15, 2002; 30(20): 4442 - 4451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-J. Hu Prediction of consensus structural motifs in a family of coregulated RNA sequences Nucleic Acids Res., September 1, 2002; 30(17): 3886 - 3893. [Abstract] [Full Text] [PDF]
|
|