{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:39:44Z","timestamp":1793403584266,"version":"4.5.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T00:00:00Z","timestamp":1545004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Muscular Dystrophy UK and Myotonic Dystrophy Support Group"},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["107562\/Z\/15\/Z"],"award-info":[{"award-number":["107562\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["262023"],"award-info":[{"award-number":["262023"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DP5OD017865"],"award-info":[{"award-number":["DP5OD017865"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS048843"],"award-info":[{"award-number":["NS048843"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL045565"],"award-info":[{"award-number":["R01HL045565"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR045653"],"award-info":[{"award-number":["R01AR045653"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RC2-HG005624"],"award-info":[{"award-number":["RC2-HG005624"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Myotonic dystrophy (dystrophia myotonica, DM) is a multi-systemic disease caused by expanded CTG or CCTG microsatellite repeats. Characterized by symptoms in muscle, heart and central nervous system, among others, it is one of the most variable diseases known. A major pathogenic event in DM is the sequestration of muscleblind-like proteins by CUG or CCUG repeat-containing RNAs transcribed from expanded repeats, and differences in the extent of MBNL sequestration dependent on repeat length and expression level may account for some portion of the variability. However, many other cellular pathways are reported to be perturbed in DM, and the severity of specific disease symptoms varies among individuals. To help understand this variability and facilitate research into DM, we generated 120 RNASeq transcriptomes from skeletal and heart muscle derived from healthy and DM1 biopsies and autopsies. A limited number of DM2 and Duchenne muscular dystrophy samples were also sequenced. We analyzed splicing and gene expression, identified tissue-specific changes in RNA processing and uncovered transcriptome changes strongly correlating with muscle strength. We created a web resource at http:\/\/DMseq.org that hosts raw and processed transcriptome data and provides a lightweight, responsive interface that enables browsing of processed data across the genome.<\/jats:p>","DOI":"10.1093\/hmg\/ddy432","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T22:44:55Z","timestamp":1544827495000},"page":"1312-1321","source":"Crossref","is-referenced-by-count":132,"title":["Transcriptome alterations in myotonic dystrophy skeletal muscle and heart"],"prefix":"10.1093","volume":"28","author":[{"given":"Eric T","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Koch Institute, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, FL, USA"},{"name":"Center for NeuroGenetics, University of Florida, Gainesville, FL, USA"},{"name":"University of Florida Genetics Institute, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Treacy","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katy","family":"Eichinger","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester, Rochester, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Struck","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Oregon, Eugene, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Estabrook","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Koch Institute, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, FL, USA"},{"name":"Center for NeuroGenetics, University of Florida, Gainesville, FL, USA"},{"name":"University of Florida Genetics Institute, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailey","family":"Olafson","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, FL, USA"},{"name":"Center for NeuroGenetics, University of Florida, Gainesville, FL, USA"},{"name":"University of Florida Genetics Institute, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas T","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirti","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester, Rochester, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Westbrook","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Queen\u2019s Medical Center, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Sedehizadeh","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Queen\u2019s Medical Center, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Neurology, Stanford University, Palo Alto, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brook","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Queen\u2019s Medical Center, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Andrew","family":"Berglund","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, FL, USA"},{"name":"Center for NeuroGenetics, University of Florida, Gainesville, FL, USA"},{"name":"University of Florida Genetics Institute, University of Florida, Gainesville, FL, USA"},{"name":"Department of Biochemistry, University of Oregon, Eugene, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, USA"},{"name":"Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Housman","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Koch Institute, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Thornton","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester, Rochester, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Burge","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Koch Institute, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,12,17]]},"reference":[{"key":"2019121022393655400_ref1","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/0092-8674(92)90154-5","article-title":"Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3\u2032 end of a transcript encoding a protein kinase family member","volume":"68","author":"Brook","year":"1992","journal-title":"Cell"},{"key":"2019121022393655400_ref2","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1126\/science.1062125","article-title":"Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9","volume":"293","author":"Liquori","year":"2001","journal-title":"Science"},{"key":"2019121022393655400_ref3","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/ana.21948","article-title":"RNA-mediated neurodegeneration in repeat expansion disorders","volume":"67","author":"Todd","year":"2010","journal-title":"Ann. Neurol."},{"key":"2019121022393655400_ref4","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.molcel.2007.07.027","article-title":"Increased steady-state levels of CUGBP1 in myotonic dystrophy 1 are due to PKC-mediated hyperphosphorylation","volume":"28","author":"Kuyumcu-Martinez","year":"2007","journal-title":"Mol. Cell"},{"key":"2019121022393655400_ref5","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1093\/hmg\/dds478","article-title":"Expanded CTG repeats trigger miRNA alterations in Drosophila that are conserved in myotonic dystrophy type 1 patients","volume":"22","author":"Fernandez-Costa","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"2019121022393655400_ref6","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/nsmb.2067","article-title":"Misregulation of miR-1 processing is associated with heart defects in myotonic dystrophy","volume":"18","author":"Rau","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2019121022393655400_ref7","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.celrep.2013.12.025","article-title":"The Mef2 transcription network is disrupted in myotonic dystrophy heart tissue, dramatically altering miRNA and mRNA expression","volume":"6","author":"Kalsotra","year":"2014","journal-title":"Cell Rep."},{"key":"2019121022393655400_ref8","doi-asserted-by":"crossref","first-page":"4461","DOI":"10.1172\/JCI64081","article-title":"GSK3\u03b2 mediates muscle pathology in myotonic dystrophy","volume":"122","author":"Jones","year":"2012","journal-title":"J. Clin. Invest."},{"key":"2019121022393655400_ref9","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1172\/JCI89616","article-title":"Targeting deregulated AMPK\/mTORC1 pathways improves muscle function in myotonic dystrophy type I","volume":"127","author":"Brockhoff","year":"2017","journal-title":"J. Clin. Invest."},{"key":"2019121022393655400_ref10","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1093\/hmg\/ddy192","article-title":"Mechanisms of skeletal muscle wasting in a mouse model for myotonic dystrophy type 1","volume":"27","author":"Morriss","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"2019121022393655400_ref11","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1073\/pnas.1013343108","article-title":"Non-ATG-initiated translation directed by microsatellite expansions","volume":"108","author":"Zu","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2019121022393655400_ref12","doi-asserted-by":"crossref","DOI":"10.1093\/hmg\/ddq427","article-title":"Expanded CTG repeat demarcates a boundary for abnormal CpG methylation in myotonic dystrophy patient tissues","volume":"20","author":"L\u00f3pez Castel","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"2019121022393655400_ref13","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.1038\/sj.emboj.7600300","article-title":"Muscleblind proteins regulate alternative splicing","volume":"23","author":"Ho","year":"2004","journal-title":"EMBO J."},{"key":"2019121022393655400_ref14","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.molcel.2014.08.027","article-title":"Loss of MBNL leads to disruption of developmentally regulated alternative polyadenylation in RNA-mediated disease","volume":"56","author":"Batra","year":"2014","journal-title":"Mol. Cell"},{"key":"2019121022393655400_ref15","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.cell.2012.06.041","article-title":"Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins","volume":"150","author":"Wang","year":"2012","journal-title":"Cell"},{"key":"2019121022393655400_ref16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S1097-2765(02)00572-5","article-title":"Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing","volume":"10","author":"Charlet","year":"2002","journal-title":"Mol. Cell"},{"key":"2019121022393655400_ref17","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S1097-2765(02)00563-4","article-title":"Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy","volume":"10","author":"Mankodi","year":"2002","journal-title":"Mol. Cell"},{"key":"2019121022393655400_ref18","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/nm.2374","article-title":"Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy","volume":"17","author":"Fugier","year":"2011","journal-title":"Nat. Med."},{"key":"2019121022393655400_ref19","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1093\/hmg\/ddr568","article-title":"Muscle weakness in myotonic dystrophy associated with misregulated splicing and altered gating of Ca(V)1.1 calcium channel","volume":"21","author":"Tang","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"2019121022393655400_ref20","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms11067","article-title":"Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy","volume":"7","author":"Freyermuth","year":"2016","journal-title":"Nat. Commun."},{"key":"2019121022393655400_ref21","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1002\/ana.23992","article-title":"Splicing biomarkers of disease severity in myotonic dystrophy","volume":"74","author":"Nakamori","year":"2013","journal-title":"Ann. Neurol."},{"key":"2019121022393655400_ref22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1006316","article-title":"Dose-dependent regulation of alternative splicing by MBNL proteins reveals biomarkers for myotonic dystrophy","volume":"12","author":"Wagner","year":"2016","journal-title":"PLoS Genet."},{"key":"2019121022393655400_ref23","doi-asserted-by":"crossref","first-page":"5885","DOI":"10.1038\/s41598-018-24156-x","article-title":"Quantitative methods to monitor RNA biomarkers in myotonic dystrophy","volume":"8","author":"Wojciechowska","year":"2018","journal-title":"Sci. Rep."},{"key":"2019121022393655400_ref24","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/nmeth.1528","article-title":"Analysis and design of RNA sequencing experiments for identifying isoform regulation","volume":"7","author":"Katz","year":"2010","journal-title":"Nat. Methods"},{"key":"2019121022393655400_ref25","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1093\/nar\/gkp1209","article-title":"MBNL1 binds GC motifs embedded in pyrimidines to regulate alternative splicing","volume":"38","author":"Goers","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2019121022393655400_ref26","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1002\/ana.22278","article-title":"Alternative splicing dysregulation secondary to skeletal muscle regeneration","volume":"69","author":"Orengo","year":"2011","journal-title":"Ann. Neurol."},{"key":"2019121022393655400_ref27","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1126\/science.280.5364.737","article-title":"Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy","volume":"280","author":"Philips","year":"1998","journal-title":"Science"},{"key":"2019121022393655400_ref28","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"2019121022393655400_ref29","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0107324","article-title":"RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1","volume":"9","author":"Klinck","year":"2014","journal-title":"PLoS One"},{"key":"2019121022393655400_ref30","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1038\/ncomms3480","article-title":"MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation","volume":"4","author":"Venables","year":"2013","journal-title":"Nat. Commun."},{"key":"2019121022393655400_ref31","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.neuron.2012.05.029","article-title":"Muscleblind-like 2-mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy","volume":"75","author":"Charizanis","year":"2012","journal-title":"Neuron"},{"key":"2019121022393655400_ref32","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1101\/gr.184390.114","article-title":"Antagonistic regulation of mRNA expression and splicing by CELF and MBNL proteins","volume":"25","author":"Wang","year":"2015","journal-title":"Genome Res."},{"key":"2019121022393655400_ref33","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/j.celrep.2015.07.029","article-title":"MBNL sequestration by toxic RNAs and RNA misprocessing in the myotonic dystrophy brain","volume":"12","author":"Goodwin","year":"2015","journal-title":"Cell Rep."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/28\/8\/1312\/28275052\/ddy432.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/28\/8\/1312\/28275052\/ddy432.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T06:54:07Z","timestamp":1720853647000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/28\/8\/1312\/5250729"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,17]]},"references-count":33,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2018,12,17]]},"published-print":{"date-parts":[[2019,4,15]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddy432","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,4,15]]},"published":{"date-parts":[[2018,12,17]]}}}