{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T21:56:29Z","timestamp":1781474189953,"version":"3.54.1"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre","doi-asserted-by":"crossref","award":["2019\/33\/B\/NZ5\/02473"],"award-info":[{"award-number":["2019\/33\/B\/NZ5\/02473"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum. Genet."],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular disorders associated with expansions of microsatellites, respectively, in <jats:italic>DMPK<\/jats:italic> and <jats:italic>CNBP<\/jats:italic>. Their pathogenesis is linked to the global aberrant alternative splicing (AAS) of many genes and marks mostly muscular and neuronal tissues, while blood is the least affected. Recent data in DM1 skeletal muscles indicated that abnormalities in RNA metabolism also include global upregulation of circular RNAs (circRNAs). CircRNAs are a heterogeneous group considered splicing errors and by-products of canonical splicing. To elucidate whether circRNA dysregulation is an inherent feature of the myotonic environment, we perform their analysis in the frontal cortex and whole blood of DM1 and DM2 patients. We find a global elevation of circRNAs in both tissues, and its magnitude is neither correlated with the differences in their parental gene expression nor is associated with AAS published earlier. Aberrantly spliced cassette exons of linear transcripts affected in DM1 and DM2 are not among the circularized exons, which unique genomic features prerequisite back-splicing. However, the blueprint of the AAS of linear RNAs is found in a variety of circRNA isoforms. The heterogeneity of circRNAs also originates from the utilization of exonic and intronic cryptic donors\/acceptors in back splice junctions, and intron-containing circRNAs are more characteristic of the blood. Overall, this study reveals circRNA dysregulation in various tissues from DM1 and DM2; however, their levels do not correlate with the AAS in linear RNAs, suggesting a potential independent regulatory mechanism underlying circRNA upregulation in myotonic dystrophy.<\/jats:p>","DOI":"10.1007\/s00439-025-02729-x","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T11:08:20Z","timestamp":1738667300000},"page":"417-432","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Global dysregulation of circular RNAs in frontal cortex and whole blood from DM1 and DM2"],"prefix":"10.1007","volume":"144","author":[{"given":"Arvind","family":"Srinivasan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Magner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Koz\u0142owski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Philips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arkadiusz","family":"Kajdasz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Wojciechowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzena","family":"Wojciechowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"issue":"7648","key":"2729_CR1","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/nature21715","volume":"544","author":"T Akta\u015f","year":"2017","unstructured":"Akta\u015f T, Av\u015far Il\u0131k \u0130, Maticzka D et al (2017) DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome. Nature 544(7648):115\u2013119","journal-title":"Nature"},{"issue":"1","key":"2729_CR2","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.molcel.2014.08.019","volume":"56","author":"R Ashwal-Fluss","year":"2014","unstructured":"Ashwal-Fluss R, Meyer M, Pamudurti NR et al (2014) CircRNA biogenesis competes with pre-mRNA splicing. Mol Cell 56(1):55\u201366","journal-title":"Mol Cell"},{"issue":"6114","key":"2729_CR3","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1126\/science.1230612","volume":"338","author":"NL Barbosa-Morais","year":"2012","unstructured":"Barbosa-Morais NL, Irimia M, Pan Q et al (2012) The evolutionary landscape of alternative splicing in vertebrate species. Science 338(6114):1587\u20131593","journal-title":"Science"},{"issue":"10","key":"2729_CR4","doi-asserted-by":"publisher","first-page":"5930","DOI":"10.1128\/MCB.18.10.5930","volume":"18","author":"MV Bell","year":"1998","unstructured":"Bell MV, Cowper AE, Lefranc MP et al (1998) Influence of intron length on alternative splicing of CD44. Mol Cell Biol 18(10):5930\u20135941","journal-title":"Mol Cell Biol"},{"issue":"11","key":"2729_CR5","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1101\/gr.177790.114","volume":"24","author":"U Braunschweig","year":"2014","unstructured":"Braunschweig U, Barbosa-Morais NL, Pan Q et al (2014) Widespread intron retention in mammals functionally tunes transcriptomes. Genome Res 24(11):1774\u20131786","journal-title":"Genome Res"},{"issue":"4","key":"2729_CR6","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/0092-8674(92)90154-5","volume":"68","author":"JD Brook","year":"1992","unstructured":"Brook JD, McCurrach ME, Harley HG et al (1992) Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3\u2019 end of a transcript encoding a protein kinase family member. Cell 68(4):799\u2013808","journal-title":"Cell"},{"issue":"2","key":"2729_CR7","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1534\/genetics.104.039701","volume":"170","author":"JM Burnette","year":"2005","unstructured":"Burnette JM, Miyamoto-Sato E, Schaub MA et al (2005) Subdivision of large introns in Drosophila by recursive splicing at nonexonic elements. Genetics 170(2):661\u2013674","journal-title":"Genetics"},{"issue":"1","key":"2729_CR8","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1186\/s12864-021-07910-w","volume":"22","author":"D Cao","year":"2021","unstructured":"Cao D (2021) Reverse complementary matches simultaneously promote both back-splicing and exon-skipping. BMC Genomics 22(1):586","journal-title":"BMC Genomics"},{"issue":"16","key":"2729_CR9","doi-asserted-by":"publisher","first-page":"7762","DOI":"10.1093\/nar\/gkv784","volume":"43","author":"Y Chen","year":"2015","unstructured":"Chen Y, Ye W, Zhang Y et al (2015) High speed BLASTN: an accelerated MegaBLAST search tool. Nucleic Acids Res 43(16):7762\u20137768","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"2729_CR10","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1093\/nar\/gkp1137","volume":"38","author":"PJ Cock","year":"2010","unstructured":"Cock PJ, Fields CJ, Goto N et al (2010) The Sanger FASTQ file format for sequences with quality scores, and the Solexa\/Illumina FASTQ variants. Nucleic Acids Res 38(6):1767\u20131771","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"2729_CR11","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1016\/j.cell.2015.02.014","volume":"160","author":"SJ Conn","year":"2015","unstructured":"Conn SJ, Pillman KA, Toubia J et al (2015) The RNA binding protein quaking regulates formation of circRNAs. Cell 160(6):1125\u20131134","journal-title":"Cell"},{"key":"2729_CR13","doi-asserted-by":"publisher","first-page":"649","DOI":"10.3389\/fgene.2019.00649","volume":"10","author":"K Czubak","year":"2019","unstructured":"Czubak K, Taylor K, Piasecka A et al (2019a) Global increase in circular RNA levels in myotonic dystrophy. Front Genet 10:649","journal-title":"Front Genet"},{"issue":"18","key":"2729_CR12","doi-asserted-by":"publisher","first-page":"4385","DOI":"10.3390\/ijms20184385","volume":"20","author":"K Czubak","year":"2019","unstructured":"Czubak K, Sedehizadeh S, Kozlowski P et al (2019b) An overview of circular RNAs and their implications in myotonic dystrophy. Int J Mol Sci 20(18):4385","journal-title":"Int J Mol Sci"},{"key":"2729_CR14","doi-asserted-by":"crossref","unstructured":"de la Mata M, Alonso CR, Kadener S et al (2003) A slow RNA polymerase II affects alternative splicing in vivo. Mol Cell. 12(2):525\u2013\u200932. 36","DOI":"10.1016\/j.molcel.2003.08.001"},{"key":"2729_CR15","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/978-1-4939-8808-2_10","volume":"1870","author":"R Dong","year":"2019","unstructured":"Dong R, Ma XK, Chen LL et al (2019) Genome-wide annotation of circRNAs and their alternative Back-Splicing\/Splicing with CIRCexplorer Pipeline. Methods Mol Biol 1870:137\u2013149","journal-title":"Methods Mol Biol"},{"issue":"1","key":"2729_CR16","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s13073-015-0168-9","volume":"7","author":"H Dvinge","year":"2015","unstructured":"Dvinge H, Bradley RK (2015) Widespread intron retention diversifies most cancer transcriptomes. Genome Med 7(1):45","journal-title":"Genome Med"},{"issue":"45","key":"2729_CR17","doi-asserted-by":"publisher","first-page":"16176","DOI":"10.1073\/pnas.0508489102","volume":"102","author":"KL Fox-Walsh","year":"2005","unstructured":"Fox-Walsh KL, Dou Y, Lam BJ et al (2005) The architecture of pre-mRNAs affects mechanisms of splice-site pairing. Proc Natl Acad Sci U S A 102(45):16176\u201316181","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"2729_CR18","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1093\/bib\/bbx014","volume":"19","author":"Y Gao","year":"2018","unstructured":"Gao Y, Zhang J, Zhao F (2018) Circular RNA identification based on multiple seed matching. Brief Bioinform 19(5):803\u2013810","journal-title":"Brief Bioinform"},{"issue":"1","key":"2729_CR19","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1101\/gr.119834.110","volume":"22","author":"S Gelfman","year":"2012","unstructured":"Gelfman S, Burstein D, Penn O et al (2012) Changes in exon-intron structure during vertebrate evolution affect the splicing pattern of exons. Genome Res 22(1):35\u201350","journal-title":"Genome Res"},{"issue":"Database issue","key":"2729_CR20","doi-asserted-by":"publisher","first-page":"D125","DOI":"10.1093\/nar\/gks997","volume":"41","author":"M Giulietti","year":"2013","unstructured":"Giulietti M, Piva F, D\u2019Antonio M et al (2013) SpliceAid-F: a database of human splicing factors and their RNA-binding sites. Nucleic Acids Res 41(Database issue):D125\u2013D131","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"2729_CR21","doi-asserted-by":"publisher","first-page":"D884","DOI":"10.1093\/nar\/gkaa942","volume":"49","author":"KL Howe","year":"2021","unstructured":"Howe KL, Achuthan P, Allen J et al (2021) Ensembl 2021. Nucleic Acids Res 49(D1):D884\u2013D891","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"2729_CR22","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1124\/molpharm.120.000225","volume":"99","author":"DG Hu","year":"2021","unstructured":"Hu DG, Mackenzie PI, Hulin JA et al (2021) Circular RNAs of UDP-Glycosyltransferase (UGT) genes Expand the Complexity and Diversity of the UGT Transcriptome. Mol Pharmacol 99(6):488\u2013503","journal-title":"Mol Pharmacol"},{"issue":"2","key":"2729_CR23","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.celrep.2014.12.019","volume":"10","author":"A Ivanov","year":"2015","unstructured":"Ivanov A, Memczak S, Wyler E et al (2015) Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep 10(2):170\u2013177","journal-title":"Cell Rep"},{"issue":"2","key":"2729_CR24","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1261\/rna.035667.112","volume":"19","author":"WR Jeck","year":"2013","unstructured":"Jeck WR, Sorrentino JA, Wang K et al (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 19(2):141\u2013157","journal-title":"RNA"},{"issue":"9","key":"2729_CR25","doi-asserted-by":"publisher","first-page":"4721","DOI":"10.1093\/nar\/gkv386","volume":"43","author":"S Kelly","year":"2015","unstructured":"Kelly S, Georgomanolis T, Zirkel A, Diermeier S et al (2015) Splicing of many human genes involves sites embedded within introns. Nucleic Acids Res 43(9):4721\u20134732","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"2729_CR26","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1093\/nar\/gkl924","volume":"35","author":"E Kim","year":"2007","unstructured":"Kim E, Magen A, Ast G (2007) Different levels of alternative splicing among eukaryotes. Nucleic Acids Res 35(1):125\u2013131","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"2729_CR27","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1007\/s00395-022-00940-9","volume":"117","author":"KE Kokot","year":"2022","unstructured":"Kokot KE, Kneuer JM, John D et al (2022) Reduction of A-to-I RNA editing in the failing human heart regulates formation of circular RNAs. Basic Res Cardiol 117(1):32","journal-title":"Basic Res Cardiol"},{"issue":"20","key":"2729_CR28","doi-asserted-by":"publisher","first-page":"2168","DOI":"10.1101\/gad.270421.115","volume":"29","author":"MC Kramer","year":"2015","unstructured":"Kramer MC, Liang D, Tatomer DC et al (2015) Combinatorial control of Drosophila circular RNA expression by intronic repeats, hnRNPs, and SR proteins. Genes Dev 29(20):2168\u20132182","journal-title":"Genes Dev"},{"issue":"1","key":"2729_CR29","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.molcel.2007.07.027","volume":"28","author":"NM Kuyumcu-Martinez","year":"2007","unstructured":"Kuyumcu-Martinez NM, Wang GS, Cooper TA (2007) Increased steady-state levels of CUGBP1 in myotonic dystrophy 1 are due to PKC-mediated hyperphosphorylation. Mol Cell 28(1):68\u201378","journal-title":"Mol Cell"},{"issue":"5","key":"2729_CR30","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/j.molcel.2014.04.016","volume":"54","author":"N Lambert","year":"2014","unstructured":"Lambert N, Robertson A, Jangi M et al (2014) RNA Bind-n-Seq: quantitative assessment of the sequence and structural binding specificity of RNA binding proteins. Mol Cell 54(5):887\u2013900","journal-title":"Mol Cell"},{"issue":"3","key":"2729_CR32","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/nsmb.2959","volume":"22","author":"Z Li","year":"2015","unstructured":"Li Z, Huang C, Bao C et al (2015) Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol 22(3):256\u2013264","journal-title":"Nat Struct Mol Biol"},{"issue":"1","key":"2729_CR31","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13059-022-02621-1","volume":"23","author":"Y Li","year":"2022","unstructured":"Li Y, Wang F, Teng P et al (2022) Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation. Genome Biol 23(1):48","journal-title":"Genome Biol"},{"issue":"20","key":"2729_CR33","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1101\/gad.251926.114","volume":"28","author":"D Liang","year":"2014","unstructured":"Liang D, Wilusz JE (2014) Short intronic repeat sequences facilitate circular RNA production. Genes Dev 28(20):2233\u20132247","journal-title":"Genes Dev"},{"issue":"5049","key":"2729_CR34","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1126\/science.1546325","volume":"255","author":"M Mahadevan","year":"1992","unstructured":"Mahadevan M, Tsilfidis C, Sabourin L et al (1992) Myotonic dystrophy mutation: an unstable CTG repeat in the 3\u2019 untranslated region of the gene. Science 255(5049):1253\u20131255","journal-title":"Science"},{"issue":"11","key":"2729_CR35","doi-asserted-by":"publisher","first-page":"1808","DOI":"10.1093\/hmg\/ddl103","volume":"15","author":"JM Margolis","year":"2006","unstructured":"Margolis JM, Schoser BG, Moseley ML et al (2006) DM2 intronic expansions: evidence for CCUG accumulation without flanking sequence or effects on ZNF9 mRNA processing or protein expression. Hum Mol Genet 15(11):1808\u20131815","journal-title":"Hum Mol Genet"},{"key":"2729_CR36","doi-asserted-by":"crossref","unstructured":"Marquez Y, H\u00f6pfler M, Ayatollahi Z et al (2015) Unmasking alternative splicing inside protein-coding exons defines exitrons and their role in proteome plasticity. Genome Res 25(7):995\u20131007","DOI":"10.1101\/gr.186585.114"},{"key":"2729_CR37","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/srep00209","volume":"2","author":"A Masuda","year":"2012","unstructured":"Masuda A, Andersen HS, Doktor TK et al (2012) CUGBP1 and MBNL1 preferentially bind to 3\u2019 UTRs and facilitate mRNA decay. Sci Rep 2:209","journal-title":"Sci Rep"},{"issue":"7441","key":"2729_CR38","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/nature11928","volume":"495","author":"S Memczak","year":"2013","unstructured":"Memczak S, Jens M, Elefsinioti A et al (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495(7441):333\u2013338","journal-title":"Nature"},{"issue":"10","key":"2729_CR39","doi-asserted-by":"publisher","first-page":"e0141214","DOI":"10.1371\/journal.pone.0141214","volume":"10","author":"S Memczak","year":"2015","unstructured":"Memczak S, Papavasileiou P, Peters O et al (2015) Identification and characterization of circular RNAs as a New Class of putative biomarkers in human blood. PLoS ONE 10(10):e0141214","journal-title":"PLoS ONE"},{"issue":"6588","key":"2729_CR40","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1126\/science.abj6987","volume":"376","author":"S Nurk","year":"2022","unstructured":"Nurk S, Koren S, Rhie A et al (2022) The complete sequence of a human genome. Science 376(6588):44\u201353","journal-title":"Science"},{"issue":"3","key":"2729_CR41","doi-asserted-by":"publisher","first-page":"108634","DOI":"10.1016\/j.celrep.2020.108634","volume":"34","author":"BA Otero","year":"2021","unstructured":"Otero BA, Poukalov K, Hildebrandt RP et al (2021) Transcriptome alterations in myotonic dystrophy frontal cortex. Cell Rep 34(3):108634","journal-title":"Cell Rep"},{"issue":"1","key":"2729_CR42","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1186\/s13104-019-4343-8","volume":"12","author":"A Piovesan","year":"2019","unstructured":"Piovesan A, Antonaros F, Vitale L et al (2019) Human protein-coding genes and gene feature statistics in 2019. BMC Res Notes 12(1):315","journal-title":"BMC Res Notes"},{"issue":"1","key":"2729_CR43","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.1038\/s41598-018-37037-0","volume":"9","author":"C Ragan","year":"2019","unstructured":"Ragan C, Goodall GJ, Shirokikh NE et al (2019) Insights into the biogenesis and potential functions of exonic circular RNA. Sci Rep 9(1):2048","journal-title":"Sci Rep"},{"key":"2729_CR44","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ymeth.2021.09.010","volume":"196","author":"K Rahimi","year":"2021","unstructured":"Rahimi K, F\u00e6rch Nielsen A, Ven\u00f8 MT et al (2021) Nanopore long-read sequencing of circRNAs. Methods 196:23\u201329","journal-title":"Methods"},{"issue":"4","key":"2729_CR45","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1093\/molbev\/msm023","volume":"24","author":"JL Rukov","year":"2007","unstructured":"Rukov JL, Irimia M, M\u00f8rk S et al (2007) High qualitative and quantitative conservation of alternative splicing in Caenorhabditis elegans and Caenorhabditis briggsae. Mol Biol Evol 24(4):909\u2013917","journal-title":"Mol Biol Evol"},{"issue":"1","key":"2729_CR46","doi-asserted-by":"publisher","first-page":"6773","DOI":"10.1038\/s41467-024-51041-1","volume":"15","author":"M Rybiczka-Te\u0161ulov","year":"2024","unstructured":"Rybiczka-Te\u0161ulov M, Garritsen O, Ven\u00f8 MT et al (2024) Circular RNAs regulate neuron size and migration of midbrain dopamine neurons during development. Nat Commun 15(1):6773","journal-title":"Nat Commun"},{"issue":"1","key":"2729_CR47","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/ng704","volume":"29","author":"RS Savkur","year":"2001","unstructured":"Savkur RS, Philips AV, Cooper TA (2001) Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet 29(1):40\u201347","journal-title":"Nat Genet"},{"issue":"1","key":"2729_CR48","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1186\/s12864-022-08820-1","volume":"23","author":"Z Shen","year":"2022","unstructured":"Shen Z, Shao YL, Liu W et al (2022) Prediction of back-splicing sites for CircRNA formation based on convolutional neural networks. BMC Genomics 23(1):581","journal-title":"BMC Genomics"},{"issue":"7552","key":"2729_CR49","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/nature14466","volume":"521","author":"CR Sibley","year":"2015","unstructured":"Sibley CR, Emmett W, Blazquez L et al (2015) Recursive splicing in long vertebrate genes. Nature 521(7552):371\u2013375","journal-title":"Nature"},{"issue":"2","key":"2729_CR50","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.tig.2003.12.004","volume":"20","author":"R Sorek","year":"2004","unstructured":"Sorek R, Shamir R, Ast G (2004) How prevalent is functional alternative splicing in the human genome? Trends Genet 20(2):68\u201371","journal-title":"Trends Genet"},{"issue":"1","key":"2729_CR51","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.celrep.2014.12.002","volume":"10","author":"S Starke","year":"2015","unstructured":"Starke S, Jost I, Rossbach O et al (2015) Exon circularization requires canonical splice signals. Cell Rep 10(1):103\u2013111","journal-title":"Cell Rep"},{"issue":"1","key":"2729_CR52","doi-asserted-by":"publisher","first-page":"6016","DOI":"10.1038\/s41598-021-85237-y","volume":"11","author":"Y Sunagawa","year":"2021","unstructured":"Sunagawa Y, Yamada S, Sonohara F et al (2021) Genome-wide identification and characterization of circular RNA in resected hepatocellular carcinoma and background liver tissue. Sci Rep 11(1):6016","journal-title":"Sci Rep"},{"issue":"1","key":"2729_CR53","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s13059-015-0690-5","volume":"16","author":"L Szabo","year":"2015","unstructured":"Szabo L, Morey R, Palpant NJ et al (2015) Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development. Genome Biol 16(1):126","journal-title":"Genome Biol"},{"issue":"1","key":"2729_CR54","doi-asserted-by":"publisher","first-page":"2022","DOI":"10.1038\/s41467-020-15962-x","volume":"11","author":"\u0141J Sznajder","year":"2020","unstructured":"Sznajder \u0141J, Scotti MM, Shin J et al (2020) Loss of MBNL1 induces RNA misprocessing in the thymus and peripheral blood. Nat Commun 11(1):2022","journal-title":"Nat Commun"},{"issue":"8","key":"2729_CR55","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.3390\/ijms20081938","volume":"20","author":"C Voellenkle","year":"2019","unstructured":"Voellenkle C, Perfetti A, Carrara M et al (2019) Dysregulation of circular RNAs in myotonic dystrophy type 1. Int J Mol Sci 20(8):1938","journal-title":"Int J Mol Sci"},{"issue":"10","key":"2729_CR59","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/nrg2164","volume":"8","author":"GS Wang","year":"2007","unstructured":"Wang GS, Cooper TA (2007) Splicing in disease: disruption of the splicing code and the decoding machinery. Nat Rev Genet 8(10):749\u2013761","journal-title":"Nat Rev Genet"},{"issue":"2","key":"2729_CR60","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.gene.2005.07.015","volume":"366","author":"M Wang","year":"2006","unstructured":"Wang M, Mar\u00edn A (2006) Characterization and prediction of alternative splice sites. Gene 366(2):219\u2013227","journal-title":"Gene"},{"issue":"7221","key":"2729_CR57","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1038\/nature07509","volume":"456","author":"ET Wang","year":"2008","unstructured":"Wang ET, Sandberg R, Luo S et al (2008) Alternative isoform regulation in human tissue transcriptomes. Nature 456(7221):470\u2013476","journal-title":"Nature"},{"issue":"4","key":"2729_CR56","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/j.cell.2012.06.041","volume":"150","author":"ET Wang","year":"2012","unstructured":"Wang ET, Cody NA, Jog S et al (2012) Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins. Cell 150(4):710\u2013724","journal-title":"Cell"},{"issue":"8","key":"2729_CR58","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1093\/hmg\/ddy432","volume":"28","author":"ET Wang","year":"2019","unstructured":"Wang ET, Treacy D, Eichinger K et al (2019) Transcriptome alterations in myotonic dystrophy skeletal muscle and heart. Hum Mol Genet 28(8):1312\u20131321","journal-title":"Hum Mol Genet"},{"issue":"15","key":"2729_CR61","doi-asserted-by":"publisher","first-page":"2411","DOI":"10.1016\/j.jmb.2015.05.019","volume":"427","author":"J Wilusz","year":"2015","unstructured":"Wilusz J (2015) Circular RNA and splicing: skip happens. J Mol Biol 427(15):2411\u20132413","journal-title":"J Mol Biol"},{"issue":"19","key":"2729_CR62","doi-asserted-by":"publisher","first-page":"3811","DOI":"10.1093\/hmg\/ddr299","volume":"20","author":"M Wojciechowska","year":"2011","unstructured":"Wojciechowska M, Krzyzosiak WJ (2011) Cellular toxicity of expanded RNA repeats: focus on RNA foci. Hum Mol Genet 20(19):3811\u20133821","journal-title":"Hum Mol Genet"},{"issue":"2\u20133","key":"2729_CR63","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1089\/1066527041410418","volume":"11","author":"G Yeo","year":"2004","unstructured":"Yeo G, Burge CB (2004) Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. J Comput Biol 11(2\u20133):377\u2013394","journal-title":"J Comput Biol"},{"issue":"11","key":"2729_CR65","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1128\/EC.05193-11","volume":"10","author":"X Zhang","year":"2011","unstructured":"Zhang X, Tolzmann CA, Melcher M et al (2011) Branch point identification and sequence requirements for intron splicing in Plasmodium Falciparum. Eukaryot Cell 10(11):1422\u20131428","journal-title":"Eukaryot Cell"},{"issue":"6","key":"2729_CR67","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.molcel.2013.08.017","volume":"51","author":"Y Zhang","year":"2013","unstructured":"Zhang Y, Zhang XO, Chen T et al (2013) Circular intronic long noncoding RNAs. Mol Cell 51(6):792\u2013806","journal-title":"Mol Cell"},{"issue":"1","key":"2729_CR66","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.cell.2014.09.001","volume":"159","author":"XO Zhang","year":"2014","unstructured":"Zhang XO, Wang HB, Zhang Y et al (2014) Complementary sequence-mediated exon circularization. Cell 159(1):134\u2013147","journal-title":"Cell"},{"issue":"44","key":"2729_CR64","doi-asserted-by":"publisher","first-page":"e2211194119","DOI":"10.1073\/pnas.2211194119","volume":"119","author":"P Zhang","year":"2022","unstructured":"Zhang P, Philippot Q, Ren W et al (2022) Genome-wide detection of human variants that disrupt intronic branchpoints. Proc Natl Acad Sci U S A 119(44):e2211194119","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"14","key":"2729_CR68","doi-asserted-by":"publisher","first-page":"e2308115","DOI":"10.1002\/advs.202308115","volume":"11","author":"Z Zhou","year":"2024","unstructured":"Zhou Z, Zhang J, Zheng X et al (2024) CIRI-Deep enables single-cell and spatial transcriptomic analysis of circular RNAs with deep learning. Adv Sci (Weinh) 11(14):e2308115","journal-title":"Adv Sci (Weinh)"}],"container-title":["Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-025-02729-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00439-025-02729-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-025-02729-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T19:02:09Z","timestamp":1744830129000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00439-025-02729-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,4]]},"references-count":68,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["2729"],"URL":"https:\/\/doi.org\/10.1007\/s00439-025-02729-x","relation":{},"ISSN":["0340-6717","1432-1203"],"issn-type":[{"value":"0340-6717","type":"print"},{"value":"1432-1203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,4]]},"assertion":[{"value":"20 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}