{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:21:53Z","timestamp":1790400113431,"version":"4.1.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2016,11,11]],"date-time":"2016-11-11T00:00:00Z","timestamp":1478822400000},"content-version":"vor","delay-in-days":1051,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ectopic modulators of alternative splicing are important tools to study the function of splice variants and for correcting mis-splicing events that cause human diseases. Such modulators can be bifunctional oligonucleotides made of an antisense portion that determines target specificity, and a non-hybridizing tail that recruits proteins or RNA\/protein complexes that affect splice site selection (TOSS and TOES, respectively, for targeted oligonucleotide silencer of splicing and targeted oligonucleotide enhancer of splicing). The use of TOSS and TOES has been restricted to a handful of targets. To generalize the applicability and demonstrate the robustness of TOSS, we have tested this approach on more than 50 alternative splicing events. Moreover, we have developed an algorithm that can design active TOSS with a success rate of 80%. To produce bifunctional oligonucleotides capable of stimulating splicing, we built on the observation that binding sites for TDP-43 can stimulate splicing and improve U1 snRNP binding when inserted downstream from 5\u2032 splice sites. A TOES designed to recruit TDP-43 improved exon 7 inclusion in SMN2. Overall, our study shows that bifunctional oligonucleotides can redirect splicing on a variety of genes, justifying their inclusion in the molecular arsenal that aims to alter the production of splice variants.<\/jats:p>","DOI":"10.1093\/nar\/gkt1287","type":"journal-article","created":{"date-parts":[[2013,12,27]],"date-time":"2013-12-27T20:30:06Z","timestamp":1388176206000},"page":"e40-e40","source":"Crossref","is-referenced-by-count":37,"title":["Redirecting splicing with bifunctional oligonucleotides"],"prefix":"10.1093","volume":"42","author":[{"given":"Jean-Philippe","family":"Brosseau","sequence":"first","affiliation":[{"name":"Laboratory of Functional Genomics and Research Centre on RNA Biology of the Universit\u00e9 de Sherbrooke 1 , Sherbrooke, Quebec J1E 4K8 , Canada"},{"name":"Department of Biochemistry, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke 2 , Sherbrooke, Quebec J1E 4K8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Lucier","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics and Research Centre on RNA Biology of the Universit\u00e9 de Sherbrooke 1 , Sherbrooke, Quebec J1E 4K8 , Canada"},{"name":"Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke 3 , Sherbrooke, Quebec J1E 4K8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9e-Anne","family":"Lamarche","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke 3 , Sherbrooke, Quebec J1E 4K8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulzim","family":"Shkreta","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke 3 , Sherbrooke, Quebec J1E 4K8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gendron","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics and Research Centre on RNA Biology of the Universit\u00e9 de Sherbrooke 1 , Sherbrooke, Quebec J1E 4K8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvy","family":"Lapointe","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics and Research Centre on RNA Biology of the Universit\u00e9 de Sherbrooke 1 , Sherbrooke, Quebec J1E 4K8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Thibault","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics and Research Centre on RNA Biology of the Universit\u00e9 de Sherbrooke 1 , Sherbrooke, Quebec J1E 4K8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9ric","family":"Paquet","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics and Research Centre on RNA Biology of the Universit\u00e9 de Sherbrooke 1 , Sherbrooke, Quebec J1E 4K8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Perreault","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics and Research Centre on RNA Biology of the Universit\u00e9 de Sherbrooke 1 , Sherbrooke, Quebec J1E 4K8 , Canada"},{"name":"Department of Biochemistry, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke 2 , Sherbrooke, Quebec J1E 4K8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif","family":"Abou Elela","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics and Research Centre on RNA Biology of the Universit\u00e9 de Sherbrooke 1 , Sherbrooke, Quebec J1E 4K8 , Canada"},{"name":"Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke 3 , Sherbrooke, Quebec J1E 4K8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Chabot","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics and Research Centre on RNA Biology of the Universit\u00e9 de Sherbrooke 1 , Sherbrooke, Quebec J1E 4K8 , Canada"},{"name":"Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke 3 , Sherbrooke, Quebec J1E 4K8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,12,26]]},"reference":[{"key":"2022080114093611500_gkt1287-B1","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/ng.259","article-title":"Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing","volume":"40","author":"Pan","year":"2008","journal-title":"Nat. Genet."},{"key":"2022080114093611500_gkt1287-B2","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nature07509","article-title":"Alternative isoform regulation in human tissue transcriptomes","volume":"456","author":"Wang","year":"2008","journal-title":"Nature"},{"key":"2022080114093611500_gkt1287-B3","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature11233","article-title":"Landscape of transcription in human cells","volume":"489","author":"Djebali","year":"2012","journal-title":"Nature"},{"key":"2022080114093611500_gkt1287-B4","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nature08909","article-title":"Expansion of the eukaryotic proteome by alternative splicing","volume":"463","author":"Nilsen","year":"2010","journal-title":"Nature"},{"key":"2022080114093611500_gkt1287-B5","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bbadis.2008.09.017","article-title":"Alternative splicing and disease","volume":"1792","author":"Tazi","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"2022080114093611500_gkt1287-B6","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/nsmb.1608","article-title":"Cancer-associated regulation of alternative splicing","volume":"16","author":"Venables","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2022080114093611500_gkt1287-B7","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1016\/j.febslet.2005.02.047","article-title":"Are splicing mutations the most frequent cause of hereditary disease?","volume":"579","author":"Lopez-Bigas","year":"2005","journal-title":"FEBS Lett."},{"key":"2022080114093611500_gkt1287-B8","doi-asserted-by":"crossref","first-page":"15974","DOI":"10.1073\/pnas.0407004101","article-title":"Identification of alternative splicing regulators by RNA interference in Drosophila","volume":"101","author":"Park","year":"2004","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022080114093611500_gkt1287-B9","doi-asserted-by":"crossref","first-page":"8673","DOI":"10.1073\/pnas.90.18.8673","article-title":"Restoration of correct splicing in thalassemic pre-mRNA by antisense oligonucleotides","volume":"90","author":"Dominski","year":"1993","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022080114093611500_gkt1287-B10","doi-asserted-by":"crossref","first-page":"17779","DOI":"10.1073\/pnas.1108482108","article-title":"Antitumorigenic potential of STAT3 alternative splicing modulation","volume":"108","author":"Zammarchi","year":"2011","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022080114093611500_gkt1287-B11","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/978-3-540-34449-0_3","article-title":"Alternative splicing: therapeutic target and tool","volume":"44","author":"Garcia-Blanco","year":"2006","journal-title":"Prog. Mol. Subcell. Biol."},{"key":"2022080114093611500_gkt1287-B12","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/nrd3625","article-title":"RNA therapeutics: beyond RNA interference and antisense oligonucleotides","volume":"11","author":"Kole","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"2022080114093611500_gkt1287-B13","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1128\/MCB.26.4.1333-1346.2006","article-title":"Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique silencer element located in the last intron","volume":"26","author":"Singh","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"2022080114093611500_gkt1287-B14","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1371\/journal.pbio.0050073","article-title":"Enhancement of SMN2 exon 7 inclusion by antisense oligonucleotides targeting the exon","volume":"5","author":"Hua","year":"2007","journal-title":"PLoS Biol."},{"key":"2022080114093611500_gkt1287-B15","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.ydbio.2011.08.025","article-title":"Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle functions","volume":"359","author":"Gallagher","year":"2011","journal-title":"Dev. Biol."},{"key":"2022080114093611500_gkt1287-B16","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1101\/gad.1941310","article-title":"Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model","volume":"24","author":"Hua","year":"2010","journal-title":"Genes Dev."},{"key":"2022080114093611500_gkt1287-B17","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nature10485","article-title":"Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model","volume":"478","author":"Hua","year":"2011","journal-title":"Nature"},{"key":"2022080114093611500_gkt1287-B18","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.ajhg.2008.01.014","article-title":"Antisense masking of an hnRNP A1\/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice","volume":"82","author":"Hua","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"2022080114093611500_gkt1287-B19","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/j.cell.2012.02.014","article-title":"Splice modulating therapies for human disease","volume":"148","author":"Spitali","year":"2012","journal-title":"Cell"},{"key":"2022080114093611500_gkt1287-B20","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/mt.2011.248","article-title":"Restoration of the dystrophin-associated glycoprotein complex after exon skipping therapy in Duchenne muscular dystrophy","volume":"20","author":"Cirak","year":"2012","journal-title":"Mol. Ther."},{"key":"2022080114093611500_gkt1287-B21","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1073\/pnas.0406700102","article-title":"Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles","volume":"102","author":"Lu","year":"2005","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022080114093611500_gkt1287-B22","doi-asserted-by":"crossref","first-page":"14814","DOI":"10.1073\/pnas.0805676105","article-title":"Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer","volume":"105","author":"Wu","year":"2008","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022080114093611500_gkt1287-B23","doi-asserted-by":"crossref","first-page":"50031","DOI":"10.1074\/jbc.M308897200","article-title":"Reprogramming alternative pre-messenger RNA splicing through the use of protein-binding antisense oligonucleotides","volume":"278","author":"Villemaire","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2022080114093611500_gkt1287-B24","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1472-6750-6-5","article-title":"Modulation of 5\u2032 splice site selection using tailed oligonucleotides carrying splicing signals","volume":"6","author":"Gendron","year":"2006","journal-title":"BMC Biotechnol."},{"key":"2022080114093611500_gkt1287-B25","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1089\/hum.2008.067","article-title":"A negatively acting bifunctional RNA increases survival motor neuron both in vitro and in vivo","volume":"19","author":"Dickson","year":"2008","journal-title":"Hum. Gene Ther."},{"key":"2022080114093611500_gkt1287-B26","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/978-0-387-77374-2_8","article-title":"hnRNP proteins and splicing control","volume":"623","author":"Martinez-Contreras","year":"2007","journal-title":"Adv. Exp. Med. Biol."},{"key":"2022080114093611500_gkt1287-B27","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/nbt964","article-title":"Alternative splicing in disease and therapy","volume":"22","author":"Garcia-Blanco","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"2022080114093611500_gkt1287-B28","doi-asserted-by":"crossref","first-page":"4114","DOI":"10.1073\/pnas.0633863100","article-title":"Bifunctional antisense oligonucleotides provide a trans-acting splicing enhancer that stimulates SMN2 gene expression in patient fibroblasts","volume":"100","author":"Skordis","year":"2003","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022080114093611500_gkt1287-B29","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/nsb887","article-title":"Correction of disease-associated exon skipping by synthetic exon-specific activators","volume":"10","author":"Cartegni","year":"2003","journal-title":"Nat. Struct. Biol."},{"key":"2022080114093611500_gkt1287-B30","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1038\/sj.mt.6300200","article-title":"Spinal muscular atrophy: SMN2 pre-mRNA splicing corrected by a U7 snRNA derivative carrying a splicing enhancer sequence","volume":"15","author":"Marquis","year":"2007","journal-title":"Mol. Ther."},{"key":"2022080114093611500_gkt1287-B31","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1128\/MCB.01174-12","article-title":"RBFOX2 is an important regulator of mesenchymal tissue-specific splicing in both normal and cancer tissues","volume":"33","author":"Venables","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"2022080114093611500_gkt1287-B32","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nsmb.2040","article-title":"Alternative splicing of SYK regulates mitosis and cell survival","volume":"18","author":"Prinos","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2022080114093611500_gkt1287-B33","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1261\/rna.1877010","article-title":"High-throughput quantification of splicing isoforms","volume":"16","author":"Brosseau","year":"2010","journal-title":"RNA"},{"key":"2022080114093611500_gkt1287-B34","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1158\/0008-5472.CAN-07-2580","article-title":"Multiple alternative splicing markers for ovarian cancer","volume":"68","author":"Klinck","year":"2008","journal-title":"Cancer Res."},{"key":"2022080114093611500_gkt1287-B35","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1128\/MCB.17.4.1776","article-title":"An intron element modulating 5\u2032 splice site selection in the hnRNP A1 pre-mRNA interacts with hnRNP A1","volume":"17","author":"Chabot","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"2022080114093611500_gkt1287-B36","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1093\/nar\/11.5.1475","article-title":"Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei","volume":"11","author":"Dignam","year":"1983","journal-title":"Nucleic Acids Res."},{"key":"2022080114093611500_gkt1287-B37","volume-title":"Ph.D. Thesis","author":"Brosseau","year":"2012"},{"key":"2022080114093611500_gkt1287-B38","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-60327-429-6_1","article-title":"UNAFold: software for nucleic acid folding and hybridization","volume":"453","author":"Markham","year":"2008","journal-title":"Methods Mol. Biol."},{"key":"2022080114093611500_gkt1287-B39","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nm1191","article-title":"Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7","volume":"11","author":"Hornung","year":"2005","journal-title":"Nat. Med."},{"key":"2022080114093611500_gkt1287-B40","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nbt1081","article-title":"Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA","volume":"23","author":"Judge","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"2022080114093611500_gkt1287-B41","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1261\/rna.28106","article-title":"Off-target effects by siRNA can induce toxic phenotype","volume":"12","author":"Fedorov","year":"2006","journal-title":"RNA"},{"key":"2022080114093611500_gkt1287-B42","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/nmeth911","article-title":"On the art of identifying effective and specific siRNAs","volume":"3","author":"Pei","year":"2006","journal-title":"Nat. Methods"},{"key":"2022080114093611500_gkt1287-B43","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"2022080114093611500_gkt1287-B44","doi-asserted-by":"crossref","first-page":"S12.11","DOI":"10.1186\/gb-2006-7-s1-s12","article-title":"AceView: a comprehensive cDNA-supported gene and transcripts annotation","volume":"7","author":"Thierry-Mieg","year":"2006","journal-title":"Genome Biol."},{"key":"2022080114093611500_gkt1287-B45","doi-asserted-by":"crossref","first-page":"e191","DOI":"10.1371\/journal.pgen.0020191","article-title":"Inference of splicing regulatory activities by sequence neighborhood analysis","volume":"2","author":"Stadler","year":"2006","journal-title":"PLoS Genet."},{"key":"2022080114093611500_gkt1287-B46","doi-asserted-by":"crossref","first-page":"36337","DOI":"10.1074\/jbc.M104236200","article-title":"Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9","volume":"276","author":"Buratti","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2022080114093611500_gkt1287-B47","doi-asserted-by":"crossref","first-page":"7353","DOI":"10.1128\/MCB.20.19.7353-7362.2000","article-title":"Control of hnRNP A1 alternative splicing: an intron element represses use of the common 3\u2032 splice site","volume":"20","author":"Simard","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"2022080114093611500_gkt1287-B48","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nsmb.1620","article-title":"Control of alternative splicing through siRNA-mediated transcriptional gene silencing","volume":"16","author":"Allo","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2022080114093611500_gkt1287-B49","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1371\/journal.pbio.0040021","article-title":"Intronic binding sites for hnRNP A\/B and hnRNP F\/H proteins stimulate pre-mRNA splicing","volume":"4","author":"Martinez-Contreras","year":"2006","journal-title":"PLoS Biol."},{"key":"2022080114093611500_gkt1287-B50","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":"Nasim","year":"2002","journal-title":"RNA"},{"key":"2022080114093611500_gkt1287-B51","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1093\/emboj\/18.7.1939","article-title":"Modulation of exon skipping by high-affinity hnRNP A1-binding sites and by intron elements that repress splice site utilization","volume":"18","author":"Blanchette","year":"1999","journal-title":"EMBO J."},{"key":"2022080114093611500_gkt1287-B52","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jmb.2011.11.003","article-title":"UG repeats\/TDP-43 interactions near 5\u2032 splice sites exert unpredictable effects on splicing modulation","volume":"415","author":"Passoni","year":"2012","journal-title":"J. Mol. Biol."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/42\/6\/e40\/45208639\/nar_42_6_e40.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/42\/6\/e40\/45208639\/nar_42_6_e40.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T10:10:31Z","timestamp":1659348631000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/42\/6\/e40\/2435196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,26]]},"references-count":52,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2013,12,26]]},"published-print":{"date-parts":[[2014,4,1]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkt1287","relation":{},"ISSN":["1362-4962","0305-1048"],"issn-type":[{"value":"1362-4962","type":"electronic"},{"value":"0305-1048","type":"print"}],"subject":[],"published-other":{"date-parts":[[2022,8,1]]},"published":{"date-parts":[[2013,12,26]]}}}