{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:16:55Z","timestamp":1791998215814,"version":"4.4.0"},"reference-count":95,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"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":["NS094393"],"award-info":[{"award-number":["NS094393"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Biomarker-driven trials hold promise for therapeutic development in chronic diseases, such as muscular dystrophy. Myotonic dystrophy type 1 (DM1) involves RNA toxicity, where transcripts containing expanded CUG-repeats (CUGexp) accumulate in nuclear foci and sequester splicing factors in the Muscleblind-like (Mbnl) family. Oligonucleotide therapies to mitigate RNA toxicity have emerged but reliable measures of target engagement are needed. Here we examined muscle transcriptomes in mouse models of DM1 and found that CUGexp expression or Mbnl gene deletion cause similar dysregulation of alternative splicing. We selected 35 dysregulated exons for further study by targeted RNA sequencing. Across a spectrum of mouse models, the individual splice events and a composite index derived from all events showed a graded response to decrements of Mbnl or increments of CUGexp. Antisense oligonucleotides caused prompt reduction of CUGexp RNA and parallel correction of the splicing index, followed by subsequent elimination of myotonia. These results suggest that targeted splice sequencing may provide a sensitive and reliable way to assess therapeutic impact in DM1.<\/jats:p>","DOI":"10.1093\/nar\/gkab022","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T03:55:28Z","timestamp":1610250928000},"page":"2240-2254","source":"Crossref","is-referenced-by-count":51,"title":["Targeted splice sequencing reveals RNA toxicity and therapeutic response in myotonic dystrophy"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4013-4321","authenticated-orcid":false,"given":"Matthew K","family":"Tanner","sequence":"first","affiliation":[{"name":"Medical Scientist Training Program, University of Rochester Medical Center, Rochester, NY\u00a014642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester Medical Center, Rochester, NY\u00a014642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A","family":"Thornton","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester Medical Center, Rochester, NY\u00a014642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"2021022716362075600_B1","first-page":"385","article-title":"Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member","volume":"69","author":"Brook","year":"1992","journal-title":"Cell"},{"key":"2021022716362075600_B2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.brainres.2014.03.039","article-title":"RNA-protein interactions in unstable microsatellite diseases","volume":"1584","author":"Mohan","year":"2014","journal-title":"Brain Res."},{"key":"2021022716362075600_B3","doi-asserted-by":"crossref","first-page":"7388","DOI":"10.1073\/pnas.94.14.7388","article-title":"Expansion of a CUG trinucleotide repeat in the 3\u2032 untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts","volume":"94","author":"Davis","year":"1997","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021022716362075600_B4","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1093\/hmg\/ddh327","article-title":"Myotonic dystrophy type 1 is associated with nuclear foci of mutant RNA, sequestration of muscleblind proteins and deregulated alternative splicing in neurons","volume":"13","author":"Jiang","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"2021022716362075600_B5","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1161\/01.RES.0000193598.89753.e3","article-title":"Nuclear RNA foci in the heart in myotonic dystrophy","volume":"97","author":"Mankodi","year":"2005","journal-title":"Circ. Res."},{"key":"2021022716362075600_B6","doi-asserted-by":"crossref","first-page":"4439","DOI":"10.1093\/emboj\/19.17.4439","article-title":"Recruitment of human muscleblind proteins to (CUG)n expansions associated with myotonic dystrophy","volume":"19","author":"Miller","year":"2000","journal-title":"EMBO J."},{"key":"2021022716362075600_B7","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1093\/hmg\/11.7.805","article-title":"Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells","volume":"11","author":"Fardaei","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"2021022716362075600_B8","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1093\/hmg\/ddl132","article-title":"Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy","volume":"15","author":"Lin","year":"2006","journal-title":"Hum. Mol. 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Heart Assoc."},{"key":"2021022716362075600_B14","doi-asserted-by":"crossref","first-page":"11067","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":"2021022716362075600_B15","doi-asserted-by":"crossref","first-page":"7205","DOI":"10.1038\/ncomms8205","article-title":"Abnormal splicing switch of DMD\u2019s penultimate exon compromises muscle fibre maintenance in myotonic dystrophy","volume":"6","author":"Rau","year":"2015","journal-title":"Nat. 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Neurol."},{"key":"2021022716362075600_B22","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1126\/science.289.5485.1769","article-title":"Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat","volume":"289","author":"Mankodi","year":"2000","journal-title":"Science"},{"key":"2021022716362075600_B23","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/nar\/gkx867","article-title":"Detection of expanded RNA repeats using thermostable group II intron reverse transcriptase","volume":"46","author":"Carrell","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2021022716362075600_B24","doi-asserted-by":"crossref","first-page":"e1003043","DOI":"10.1371\/journal.pgen.1003043","article-title":"Molecular, physiological, and motor performance defects in DMSXL mice carrying&gt;1,000 CTG repeats from the human DM1 locus","volume":"8","author":"Huguet","year":"2012","journal-title":"PLoS Genet."},{"key":"2021022716362075600_B25","doi-asserted-by":"crossref","first-page":"C1291","DOI":"10.1152\/ajpcell.00336.2006","article-title":"Chloride channelopathy in myotonic dystrophy resulting from loss of posttranscriptional regulation for CLCN1","volume":"292","author":"Lueck","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2021022716362075600_B26","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"2021022716362075600_B27","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: a fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"2021022716362075600_B28","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1038\/nprot.2016.095","article-title":"Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown","volume":"11","author":"Pertea","year":"2016","journal-title":"Nat. Protoc."},{"key":"2021022716362075600_B29","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"2021022716362075600_B30","doi-asserted-by":"crossref","first-page":"E5593","DOI":"10.1073\/pnas.1419161111","article-title":"rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data","volume":"111","author":"Shen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. 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Cell"},{"key":"2021022716362075600_B36","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nsmb.1720","article-title":"Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy","volume":"17","author":"Du","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2021022716362075600_B37","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":"2021022716362075600_B38","doi-asserted-by":"crossref","first-page":"9119","DOI":"10.1093\/nar\/gky565","article-title":"MBNL splicing activity depends on RNA binding site structural context","volume":"46","author":"Taylor","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2021022716362075600_B39","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1261\/rna.038422.113","article-title":"Quaking and PTB control overlapping splicing regulatory networks during muscle cell differentiation","volume":"19","author":"Hall","year":"2013","journal-title":"RNA"},{"key":"2021022716362075600_B40","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1093\/hmg\/ddp058","article-title":"Transcriptional and post-transcriptional impact of toxic RNA in myotonic dystrophy","volume":"18","author":"Osborne","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"2021022716362075600_B41","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1006\/dbio.1995.0002","article-title":"Regulation of muscle differentiation by the MEF2 family of MADS box transcription factors","volume":"172","author":"Olson","year":"1995","journal-title":"Dev. Biol."},{"key":"2021022716362075600_B42","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev.cellbio.14.1.167","article-title":"Transcriptional control of muscle development by myocyte enhancer factor-2 (MEF2) proteins","volume":"14","author":"Black","year":"1998","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2021022716362075600_B43","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1101\/gad.215400.113","article-title":"Tissue-specific splicing of a ubiquitously expressed transcription factor is essential for muscle differentiation","volume":"27","author":"Sebastian","year":"2013","journal-title":"Genes Dev."},{"key":"2021022716362075600_B44","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1074\/jbc.M114.606277","article-title":"Alternative splicing of MEF2C pre-mRNA controls its activity in normal myogenesis and promotes tumorigenicity in rhabdomyosarcoma cells","volume":"290","author":"Zhang","year":"2015","journal-title":"J. Biol. Chem."},{"key":"2021022716362075600_B45","doi-asserted-by":"crossref","first-page":"34518","DOI":"10.1074\/jbc.M110.104133","article-title":"Proline isomerase Pin1 represses terminal differentiation and myocyte enhancer factor 2C function in skeletal muscle cells","volume":"285","author":"Magli","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2021022716362075600_B46","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1080\/15384101.2015.1026519","article-title":"Phosphorylation-dependent degradation of MEF2C contributes to regulate G2\/M transition","volume":"14","author":"Badodi","year":"2015","journal-title":"Cell Cycle"},{"key":"2021022716362075600_B47","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1002\/stem.2495","article-title":"Dynamic phosphorylation of the myocyte enhancer factor 2C\u03b11 splice variant promotes skeletal muscle regeneration and hypertrophy","volume":"35","author":"Baruffaldi","year":"2017","journal-title":"Stem Cells"},{"key":"2021022716362075600_B48","doi-asserted-by":"crossref","first-page":"e1006316","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":"2021022716362075600_B49","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1093\/hmg\/ddy432","article-title":"Transcriptome alterations in myotonic dystrophy skeletal muscle and heart","volume":"28","author":"Wang","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"2021022716362075600_B50","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ceca.2008.11.005","article-title":"Alternative splicing of RyR1 alters the efficacy of skeletal EC coupling","volume":"45","author":"Kimura","year":"2009","journal-title":"Cell Calc."},{"key":"2021022716362075600_B51","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1085\/jgp.200609635","article-title":"Muscle chloride channel dysfunction in two mouse models of myotonic dystrophy","volume":"129","author":"Lueck","year":"2007","journal-title":"J. Gen. Physiol."},{"key":"2021022716362075600_B52","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1101\/gad.300590.117","article-title":"Disrupted prenatal RNA processing and myogenesis in congenital myotonic dystrophy","volume":"31","author":"Thomas","year":"2017","journal-title":"Genes Dev."},{"key":"2021022716362075600_B53","doi-asserted-by":"crossref","first-page":"20333","DOI":"10.1073\/pnas.0809045105","article-title":"A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart","volume":"105","author":"Kalsotra","year":"2008","journal-title":"Proc. Natl. Acad. Sci. 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Morphol."},{"key":"2021022716362075600_B57","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S0248-4900(03)00087-X","article-title":"Myosin heavy chain isoforms in postnatal muscle development of mice","volume":"95","author":"Agbulut","year":"2003","journal-title":"Biol. Cell"},{"key":"2021022716362075600_B58","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":"2021022716362075600_B59","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1083\/jcb.111.6.2437","article-title":"Normal myogenic cells from newborn mice restore normal histology to degenerating muscles of the mdx mouse","volume":"111","author":"Morgan","year":"1990","journal-title":"J. Cell Biol."},{"key":"2021022716362075600_B60","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13395-015-0041-y","article-title":"Muscular dystrophy in the mdx mouse is a severe myopathy compounded by hypotrophy, hypertrophy and hyperplasia","volume":"5","author":"Duddy","year":"2015","journal-title":"Skelet. Muscle"},{"key":"2021022716362075600_B61","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3389\/fnins.2011.00141","article-title":"Depolarization-mediated regulation of alternative splicing","volume":"5","author":"Sharma","year":"2011","journal-title":"Front. Neurosci."},{"key":"2021022716362075600_B62","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1172\/JCI0215417","article-title":"Activation of the MEF2 transcription factor in skeletal muscles from myotonic mice","volume":"109","author":"Wu","year":"2002","journal-title":"J. Clin. Invest."},{"key":"2021022716362075600_B63","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/mus.880110504","article-title":"The myotonic mouse mutant ADR: physiological and histochemical properties of muscle","volume":"11","author":"Reininghaus","year":"1988","journal-title":"Muscle Nerve"},{"key":"2021022716362075600_B64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15476286.2017.1384119","article-title":"MBNL expression in autoregulatory feedback loops","volume":"15","author":"Konieczny","year":"2018","journal-title":"RNA Biol"},{"key":"2021022716362075600_B65","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1093\/nar\/gkw1158","article-title":"Autoregulation of MBNL1 function by exon 1 exclusion from MBNL1 transcript","volume":"45","author":"Konieczny","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2021022716362075600_B66","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1093\/hmg\/ddw042","article-title":"A low absolute number of expanded transcripts is involved in myotonic dystrophy type 1 manifestation in muscle","volume":"25","author":"Gudde","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"2021022716362075600_B67","doi-asserted-by":"crossref","first-page":"e52","DOI":"10.1371\/journal.pgen.0030052","article-title":"CTG trinucleotide repeat \u201cbig jumps\u201d: large expansions, small mice","volume":"3","author":"Gomes-Pereira","year":"2007","journal-title":"PLoS Genet."},{"key":"2021022716362075600_B68","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1038\/s41467-018-04892-4","article-title":"miR-23b and miR-218 silencing increase Muscleblind-like expression and alleviate myotonic dystrophy phenotypes in mammalian models","volume":"9","author":"Cerro-Herreros","year":"2018","journal-title":"Nat. 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Biol."},{"key":"2021022716362075600_B72","doi-asserted-by":"crossref","first-page":"4461","DOI":"10.1172\/JCI64081","article-title":"GSK3beta mediates muscle pathology in myotonic dystrophy","volume":"122","author":"Jones","year":"2012","journal-title":"J. Clin. Invest."},{"key":"2021022716362075600_B73","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":"2021022716362075600_B74","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1093\/hmg\/ddu617","article-title":"TWEAK\/Fn14, a pathway and novel therapeutic target in myotonic dystrophy","volume":"24","author":"Yadava","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"2021022716362075600_B75","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1073\/pnas.1013343108","article-title":"Non-ATG\u2013initiated translation directed by microsatellite expansions","volume":"108","author":"Zu","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021022716362075600_B76","doi-asserted-by":"crossref","first-page":"4271","DOI":"10.1038\/sj.emboj.7601296","article-title":"Interaction of musleblind, CUG-BP1 and hnRNP H proteins in DM1-associated aberrant IR splicing","volume":"25","author":"Paul","year":"2006","journal-title":"EMBO J."},{"key":"2021022716362075600_B77","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":"2021022716362075600_B78","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":"2021022716362075600_B79","doi-asserted-by":"crossref","first-page":"e107324","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":"2021022716362075600_B80","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1152\/physrev.00031.2010","article-title":"Fiber types in mammalian skeletal muscles","volume":"91","author":"Schiaffino","year":"2011","journal-title":"Physiol. Rev."},{"key":"2021022716362075600_B81","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1002\/(SICI)1521-1878(200006)22:6<510::AID-BIES4>3.0.CO;2-1","article-title":"Remodeling muscles with calcineurin","volume":"22","author":"Olson","year":"2000","journal-title":"Bioessays"},{"key":"2021022716362075600_B82","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1242\/jcs.02404","article-title":"Colocalization of muscleblind with RNA foci is separable from mis-regulation of alternative splicing in myotonic dystrophy","volume":"118","author":"Ho","year":"2005","journal-title":"J. Cell Sci."},{"key":"2021022716362075600_B83","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1242\/jcs.073270","article-title":"Stochastic and reversible aggregation of mRNA with expanded CUG-triplet repeats","volume":"124","author":"Querido","year":"2011","journal-title":"J. Cell Sci."},{"key":"2021022716362075600_B84","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nature22386","article-title":"RNA phase transitions in repeat expansion disorders","volume":"546","author":"Jain","year":"2017","journal-title":"Nature"},{"key":"2021022716362075600_B85","doi-asserted-by":"crossref","first-page":"10873","DOI":"10.1093\/nar\/gku767","article-title":"MBNL proteins and their target RNAs, interaction and splicing regulation","volume":"42","author":"Konieczny","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2021022716362075600_B86","doi-asserted-by":"crossref","first-page":"5773","DOI":"10.1074\/jbc.M410781200","article-title":"MBNL1 is the primary determinant of focus formation and aberrant insulin receptor splicing in DM1","volume":"280","author":"Dansithong","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2021022716362075600_B87","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1126\/science.1173110","article-title":"Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA","volume":"325","author":"Wheeler","year":"2009","journal-title":"Science"},{"key":"2021022716362075600_B88","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1093\/nar\/gkw065","article-title":"RNA cleavage products generated by antisense oligonucleotides and siRNAs are processed by the RNA surveillance machinery","volume":"44","author":"Lima","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2021022716362075600_B89","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1101\/gr.130559.111","article-title":"Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals","volume":"22","author":"Tani","year":"2012","journal-title":"Genome Res."},{"key":"2021022716362075600_B90","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1093\/nar\/gkp542","article-title":"Conserved principles of mammalian transcriptional regulation revealed by RNA half-life","volume":"37","author":"Friedel","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2021022716362075600_B91","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1172\/JCI113570","article-title":"Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans","volume":"82","author":"Nair","year":"1988","journal-title":"J. Clin. Invest."},{"key":"2021022716362075600_B92","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/ana.410170115","article-title":"In vivo estimation of muscle protein synthesis in myotonic dystrophy","volume":"17","author":"Halliday","year":"1985","journal-title":"Ann. Neurol."},{"key":"2021022716362075600_B93","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1212\/01.WNL.0000148482.40683.88","article-title":"Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current","volume":"63","author":"Berg","year":"2004","journal-title":"Neurology"},{"key":"2021022716362075600_B94","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1085\/jgp.20028741","article-title":"Involvement of helices at the dimer interface in ClC-1 common gating","volume":"121","author":"Duffield","year":"2003","journal-title":"J. Gen. 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