{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:02:46Z","timestamp":1790895766058,"version":"4.1.0"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2009,3,6]],"date-time":"2009-03-06T00:00:00Z","timestamp":1236297600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1000300","type":"journal-article","created":{"date-parts":[[2009,3,5]],"date-time":"2009-03-05T20:54:18Z","timestamp":1236286458000},"page":"e1000300","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":53,"title":["Alu Exonization Events Reveal Features Required for Precise Recognition of Exons by the Splicing Machinery"],"prefix":"10.1371","volume":"5","author":[{"given":"Schraga","family":"Schwartz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurit","family":"Gal-Mark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nir","family":"Kfir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Oren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil","family":"Ast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2009,3,6]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev.biochem.72.121801.161720","article-title":"Mechanisms of alternative pre-messenger RNA splicing.","volume":"72","author":"DL Black","year":"2003","journal-title":"Annu Rev Biochem"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/S0955-0674(00)00212-X","article-title":"Pre-mRNA splicing in the new millennium.","volume":"13","author":"ML Hastings","year":"2001","journal-title":"Curr Opin Cell Biol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1074\/jbc.270.6.2411","article-title":"Exon recognition in vertebrate splicing.","volume":"270","author":"SM Berget","year":"1995","journal-title":"J Biol Chem"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"16176","DOI":"10.1073\/pnas.0508489102","article-title":"The architecture of pre-mRNAs affects mechanisms of splice-site pairing.","volume":"102","author":"KL Fox-Walsh","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/0092-8674(85)90239-9","article-title":"Alternative splicing caused by RNA secondary structure.","volume":"43","author":"D Solnick","year":"1985","journal-title":"Cell"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1126\/science.2063195","article-title":"RNA secondary structure repression of a muscle-specific exon in HeLa cell nuclear extracts.","volume":"252","author":"B Clouet d'Orval","year":"1991","journal-title":"Science"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1126\/science.2063196","article-title":"Tissue-specific splicing in vivo of the beta-tropomyosin gene: dependence on an RNA secondary structure.","volume":"252","author":"D Libri","year":"1991","journal-title":"Science"},{"key":"ref8","first-page":"405","article-title":"A highly stable duplex structure sequesters the 5\u2032 splice site region of hnRNP A1 alternative exon 7B.","volume":"3","author":"M Blanchette","year":"1997","journal-title":"RNA"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"15134","DOI":"10.1074\/jbc.274.21.15134","article-title":"5\u2032 Splice site mutations in tau associated with the inherited dementia FTDP-17 affect a stem-loop structure that regulates alternative splicing of exon 10.","volume":"274","author":"A Grover","year":"1999","journal-title":"J Biol Chem"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"10505","DOI":"10.1128\/MCB.24.24.10505-10514.2004","article-title":"Influence of RNA secondary structure on the pre-mRNA splicing process.","volume":"24","author":"E Buratti","year":"2004","journal-title":"Mol Cell Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"4369","DOI":"10.1093\/nar\/gkm447","article-title":"RNA structure is a key regulatory element in pathological ATM and CFTR pseudoexon inclusion events.","volume":"35","author":"E Buratti","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1093\/nar\/gkl1050","article-title":"Modulating role of RNA structure in alternative splicing of a critical exon in the spinal muscular atrophy genes.","volume":"35","author":"NN Singh","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"6338","DOI":"10.1093\/nar\/gki923","article-title":"Statistical evidence for conserved, local secondary structure in the coding regions of eukaryotic mRNAs and pre-mRNAs.","volume":"33","author":"IM Meyer","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"e204","DOI":"10.1371\/journal.pgen.0030204","article-title":"Pre-mRNA secondary structures influence exon recognition.","volume":"3","author":"M Hiller","year":"2007","journal-title":"PLoS Genet"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1261\/rna.1069408","article-title":"Conserved RNA secondary structures promote alternative splicing.","volume":"14","author":"PJ Shepard","year":"2008","journal-title":"RNA"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/bies.20692","article-title":"Alternative splicing: current perspectives.","volume":"30","author":"E Kim","year":"2008","journal-title":"Bioessays"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1101\/gad.1195304","article-title":"Computational definition of sequence motifs governing constitutive exon splicing.","volume":"18","author":"XH Zhang","year":"2004","journal-title":"Genes Dev"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1101\/gr.1679003","article-title":"Sequence information for the splicing of human pre-mRNA identified by support vector machine classification.","volume":"13","author":"XH Zhang","year":"2003","journal-title":"Genome Res"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"R127","DOI":"10.1186\/gb-2007-8-6-r127","article-title":"Comparative analysis of transposed element insertion within human and mouse genomes reveals Alu's unique role in shaping the human transcriptome.","volume":"8","author":"N Sela","year":"2007","journal-title":"Genome Biol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-5793(97)01259-3","article-title":"Alu sequences.","volume":"417","author":"AJ Mighell","year":"1997","journal-title":"FEBS Lett"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.tig.2007.02.002","article-title":"Evolutionary history of 7SL RNA-derived SINEs in Supraprimates.","volume":"23","author":"JO Kriegs","year":"2007","journal-title":"Trends Genet"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1093\/nar\/gkn024","article-title":"Alternative splicing of Alu exons\u2014two arms are better than one.","volume":"36","author":"N Gal-Mark","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1101\/gr.229302","article-title":"Alu-containing exons are alternatively spliced.","volume":"12","author":"R Sorek","year":"2002","journal-title":"Genome Res"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1126\/science.1082588","article-title":"The birth of an alternatively spliced exon: 3\u2032 splice-site selection in Alu exons.","volume":"300","author":"G Lev-Maor","year":"2003","journal-title":"Science"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nrg1896","article-title":"Alternative splicing and RNA selection pressure\u2014evolutionary consequences for eukaryotic genomes.","volume":"7","author":"Y Xing","year":"2006","journal-title":"Nat Rev Genet"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S1097-2765(04)00181-9","article-title":"Minimal conditions for exonization of intronic sequences: 5\u2032 splice site formation in alu exons.","volume":"14","author":"R Sorek","year":"2004","journal-title":"Mol Cell"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1101\/gr.6320607","article-title":"Functional persistence of exonized mammalian-wide interspersed repeat elements (MIRs).","volume":"17","author":"M Krull","year":"2007","journal-title":"Genome Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"3513","DOI":"10.1128\/MCB.02279-07","article-title":"Multifactorial interplay controls the splicing profile of Alu-derived exons.","volume":"28","author":"O Ram","year":"2008","journal-title":"Mol Cell Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.1093\/nar\/gkg599","article-title":"Vienna RNA secondary structure server.","volume":"31","author":"IL Hofacker","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1093\/nar\/29.2.464","article-title":"Conserved stem-loop structures in the HIV-1 RNA region containing the A3 3\u2032 splice site and its cis-regulatory element: possible involvement in RNA splicing.","volume":"29","author":"S Jacquenet","year":"2001","journal-title":"Nucleic Acids Res"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"e117","DOI":"10.1093\/nar\/gkl544","article-title":"Using RNA secondary structures to guide sequence motif finding towards single-stranded regions.","volume":"34","author":"M Hiller","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"R141","DOI":"10.1186\/gb-2008-9-9-r141","article-title":"Exon creation and establishment in human genes.","volume":"9","author":"A Corvelo","year":"2008","journal-title":"Genome Biol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"6399","DOI":"10.1093\/nar\/gkm680","article-title":"Global control of aberrant splice-site activation by auxiliary splicing sequences: evidence for a gradient in exon and intron definition.","volume":"35","author":"J Kralovicova","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"5053","DOI":"10.1093\/nar\/gki810","article-title":"Distribution of SR protein exonic splicing enhancer motifs in human protein-coding genes.","volume":"33","author":"J Wang","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.1093\/nar\/gkg616","article-title":"ESEfinder: A web resource to identify exonic splicing enhancers.","volume":"31","author":"L Cartegni","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1126\/science.1073774","article-title":"Predictive identification of exonic splicing enhancers in human genes.","volume":"297","author":"WG Fairbrother","year":"2002","journal-title":"Science"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.molcel.2006.05.008","article-title":"Comparative analysis identifies exonic splicing regulatory sequences\u2014the complex definition of enhancers and silencers.","volume":"22","author":"A Goren","year":"2006","journal-title":"Mol Cell"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.cell.2004.11.010","article-title":"Systematic identification and analysis of exonic splicing silencers.","volume":"119","author":"Z Wang","year":"2004","journal-title":"Cell"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1093\/bioinformatics\/bti132","article-title":"Accurate identification of alternatively spliced exons using support vector machine.","volume":"21","author":"G Dror","year":"2005","journal-title":"Bioinformatics"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev.bi.62.070193.001445","article-title":"hnRNP proteins and the biogenesis of mRNA.","volume":"62","author":"G Dreyfuss","year":"1993","journal-title":"Annu Rev Biochem"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/0092-8674(88)90202-4","article-title":"Effects of RNA secondary structure on alternative splicing of pre-mRNA: is folding limited to a region behind the transcribing RNA polymerase?","volume":"54","author":"LP Eperon","year":"1988","journal-title":"Cell"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1128\/MCB.19.4.2657","article-title":"Regulation of fibronectin EDA exon alternative splicing: possible role of RNA secondary structure for enhancer display.","volume":"19","author":"AF Muro","year":"1999","journal-title":"Mol Cell Biol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1017\/S1355838202024056","article-title":"High-affinity hnRNP A1 binding sites and duplex-forming inverted repeats have similar effects on 5\u2032 splice site selection in support of a common looping out and repression mechanism.","volume":"8","author":"FU Nasim","year":"2002","journal-title":"RNA"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1261\/rna.2040605","article-title":"Determinants of the inherent strength of human 5\u2032 splice sites.","volume":"11","author":"X Roca","year":"2005","journal-title":"RNA"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nrg1451","article-title":"How did alternative splicing evolve?","volume":"5","author":"G Ast","year":"2004","journal-title":"Nat Rev Genet"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1261\/rna.1024908","article-title":"The effect of intron length on exon creation ratios during the evolution of mammalian genomes.","volume":"14","author":"M Roy","year":"2008","journal-title":"RNA"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"11222","DOI":"10.1016\/S0021-9258(18)82114-7","article-title":"A mutational analysis of the polypyrimidine tract of introns. Effects of sequence differences in pyrimidine tracts on splicing.","volume":"268","author":"RF Roscigno","year":"1993","journal-title":"J Biol Chem"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"13427","DOI":"10.1073\/pnas.0603042103","article-title":"Comparison of multiple vertebrate genomes reveals the birth and evolution of human exons.","volume":"103","author":"XH Zhang","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1101\/gr.2572604","article-title":"A non-EST-based method for exon-skipping prediction.","volume":"14","author":"R Sorek","year":"2004","journal-title":"Genome Res"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1093\/bib\/bbl015","article-title":"A hitchhiker's guide to expressed sequence tag (EST) analysis.","volume":"8","author":"SH Nagaraj","year":"2007","journal-title":"Brief Bioinform"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"D47","DOI":"10.1093\/nar\/gkm949","article-title":"TranspoGene and microTranspoGene: transposed elements influence on the transcriptome of seven vertebrates and invertebrates.","volume":"36","author":"A Levy","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref52","first-page":"1","article-title":"An overview of squence comparison.","author":"JB Kruskal","year":"1983"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1159\/000084979","article-title":"Repbase Update, a database of eukaryotic repetitive elements.","volume":"110","author":"J Jurka","year":"2005","journal-title":"Cytogenet Genome Res"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"7155","DOI":"10.1093\/nar\/15.17.7155","article-title":"RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression.","volume":"15","author":"MB Shapiro","year":"1987","journal-title":"Nucleic Acids Res"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1101\/gr.6818908","article-title":"Large-scale comparative analysis of splicing signals and their corresponding splicing factors in eukaryotes.","volume":"18","author":"SH Schwartz","year":"2008","journal-title":"Genome Res"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/BF00818163","article-title":"Fast folding and comparison of RNA secondary structures.","volume":"125","author":"IL Hofacker","year":"1994","journal-title":"Monatsh Chem"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1073\/pnas.0409169102","article-title":"Fast and reliable prediction of noncoding RNAs.","volume":"102","author":"S Washietl","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1101\/gr.1257503","article-title":"Widespread selection for local RNA secondary structure in coding regions of bacterial genes.","volume":"13","author":"L Katz","year":"2003","journal-title":"Genome Res"},{"key":"ref59","article-title":"e1071: Misc Functions of the Department of Statistics (e1071), TU Wien","author":"E Dimitriadou","year":"2007"},{"key":"ref60","article-title":"LIBSVM: A Library for Support Vector Machines.","author":"C-C Chang","year":"2001"},{"key":"ref61","article-title":"R: A Language and Environment for Statistical Computing","year":"2007"},{"key":"ref62","first-page":"3940","article-title":"ROCR: visualizing classifier performance in R. Bioinformatics","volume":"21","author":"T Sing","year":"2005"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000300","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T15:36:20Z","timestamp":1633188980000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000300"}},"subtitle":[],"editor":[{"given":"Roderic","family":"Guig\u00f3","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2009,3,6]]},"references-count":62,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2009,3,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000300","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3,6]]}}}