Mbnl1

Summary

Gene Symbol: Mbnl1
Description: muscleblind like splicing factor 1
Alias: Mbnl, mKIAA0428, muscleblind-like protein 1, muscleblind-like 1, triplet-expansion RNA-binding protein
Species: mouse
Products:     Mbnl1

Top Publications

  1. Batra R, Charizanis K, Manchanda M, Mohan A, Li M, Finn D, et al. Loss of MBNL leads to disruption of developmentally regulated alternative polyadenylation in RNA-mediated disease. Mol Cell. 2014;56:311-322 pubmed publisher
    ..Although MBNL1 and MBNL2 bind to nascent transcripts to regulate alternative splicing during muscle and brain development, ..
  2. Lin X, Miller J, Mankodi A, Kanadia R, Yuan Y, Moxley R, et al. Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy. Hum Mol Genet. 2006;15:2087-97 pubmed
    ..The repeat-bearing transcripts accumulate in nuclear foci, together with proteins in the muscleblind family, MBNL1 and MBNL2...
  3. Lueck J, Mankodi A, Swanson M, Thornton C, Dirksen R. Muscle chloride channel dysfunction in two mouse models of myotonic dystrophy. J Gen Physiol. 2007;129:79-94 pubmed
    ..Qualitatively similar results were observed for ClC-1 channel activity in knockout mice for muscleblind-like 1 (Mbnl1(DeltaE3/DeltaE3)), a second murine model of DM1 that exhibits prominent myotonia and altered Clcn1 splicing (..
  4. Matynia A, Ng C, Dansithong W, Chiang A, Silva A, Reddy S. Muscleblind1, but not Dmpk or Six5, contributes to a complex phenotype of muscular and motivational deficits in mouse models of myotonic dystrophy. PLoS ONE. 2010;5:e9857 pubmed publisher
    ..Decreased levels of DMPK (Dystrophia Myotonica-protein kinase), SIX5, a transcription factor or MBNL1 (Muscleblind-like 1), an RNA splice regulator have been demonstrated to contribute to distinct features of cDM1...
  5. Du H, Cline M, Osborne R, Tuttle D, Clark T, Donohue J, et al. Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy. Nat Struct Mol Biol. 2010;17:187-93 pubmed publisher
    ..two mouse models of DM1, one expressing a CTG(exp) transgene and another homozygous for a defective muscleblind 1 (Mbnl1) gene...
  6. Kanadia R, Urbinati C, Crusselle V, Luo D, Lee Y, Harrison J, et al. Developmental expression of mouse muscleblind genes Mbnl1, Mbnl2 and Mbnl3. Gene Expr Patterns. 2003;3:459-62 pubmed
    ..from the affected genes sequester a family of double-stranded RNA-binding factors, the muscleblind proteins MBNL1, MBNL2 and MBNL3, in the nucleus...
  7. Kanadia R, Johnstone K, Mankodi A, Lungu C, Thornton C, Esson D, et al. A muscleblind knockout model for myotonic dystrophy. Science. 2003;302:1978-80 pubmed
    ..Here, we show that disruption of the mouse Mbnl1 gene leads to muscle, eye, and RNA splicing abnormalities that are characteristic of DM disease...
  8. Lee K, Li M, Manchanda M, Batra R, Charizanis K, Mohan A, et al. Compound loss of muscleblind-like function in myotonic dystrophy. EMBO Mol Med. 2013;5:1887-900 pubmed publisher
    ..While these mutant RNAs inhibit MBNL1 splicing activity in heart and skeletal muscles, Mbnl1 knockout mice fail to recapitulate the full-range of DM ..
  9. Suenaga K, Lee K, Nakamori M, Tatsumi Y, Takahashi M, Fujimura H, et al. Muscleblind-like 1 knockout mice reveal novel splicing defects in the myotonic dystrophy brain. PLoS ONE. 2012;7:e33218 pubmed publisher
    ..In skeletal muscle, nuclear sequestration of the alternative splicing factor muscleblind-like 1 (MBNL1) explains the majority of the alternative splicing defects observed in the HSA(LR) transgenic mouse model which ..
  10. Wang E, Cody N, Jog S, Biancolella M, Wang T, Treacy D, et al. Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins. Cell. 2012;150:710-24 pubmed publisher
    ..events whose regulation depended on Mbnl function in a pattern indicating functional interchangeability between Mbnl1 and Mbnl2...

Detail Information

Publications44

  1. Batra R, Charizanis K, Manchanda M, Mohan A, Li M, Finn D, et al. Loss of MBNL leads to disruption of developmentally regulated alternative polyadenylation in RNA-mediated disease. Mol Cell. 2014;56:311-322 pubmed publisher
    ..Although MBNL1 and MBNL2 bind to nascent transcripts to regulate alternative splicing during muscle and brain development, ..
  2. Lin X, Miller J, Mankodi A, Kanadia R, Yuan Y, Moxley R, et al. Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy. Hum Mol Genet. 2006;15:2087-97 pubmed
    ..The repeat-bearing transcripts accumulate in nuclear foci, together with proteins in the muscleblind family, MBNL1 and MBNL2...
  3. Lueck J, Mankodi A, Swanson M, Thornton C, Dirksen R. Muscle chloride channel dysfunction in two mouse models of myotonic dystrophy. J Gen Physiol. 2007;129:79-94 pubmed
    ..Qualitatively similar results were observed for ClC-1 channel activity in knockout mice for muscleblind-like 1 (Mbnl1(DeltaE3/DeltaE3)), a second murine model of DM1 that exhibits prominent myotonia and altered Clcn1 splicing (..
  4. Matynia A, Ng C, Dansithong W, Chiang A, Silva A, Reddy S. Muscleblind1, but not Dmpk or Six5, contributes to a complex phenotype of muscular and motivational deficits in mouse models of myotonic dystrophy. PLoS ONE. 2010;5:e9857 pubmed publisher
    ..Decreased levels of DMPK (Dystrophia Myotonica-protein kinase), SIX5, a transcription factor or MBNL1 (Muscleblind-like 1), an RNA splice regulator have been demonstrated to contribute to distinct features of cDM1...
  5. Du H, Cline M, Osborne R, Tuttle D, Clark T, Donohue J, et al. Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy. Nat Struct Mol Biol. 2010;17:187-93 pubmed publisher
    ..two mouse models of DM1, one expressing a CTG(exp) transgene and another homozygous for a defective muscleblind 1 (Mbnl1) gene...
  6. Kanadia R, Urbinati C, Crusselle V, Luo D, Lee Y, Harrison J, et al. Developmental expression of mouse muscleblind genes Mbnl1, Mbnl2 and Mbnl3. Gene Expr Patterns. 2003;3:459-62 pubmed
    ..from the affected genes sequester a family of double-stranded RNA-binding factors, the muscleblind proteins MBNL1, MBNL2 and MBNL3, in the nucleus...
  7. Kanadia R, Johnstone K, Mankodi A, Lungu C, Thornton C, Esson D, et al. A muscleblind knockout model for myotonic dystrophy. Science. 2003;302:1978-80 pubmed
    ..Here, we show that disruption of the mouse Mbnl1 gene leads to muscle, eye, and RNA splicing abnormalities that are characteristic of DM disease...
  8. Lee K, Li M, Manchanda M, Batra R, Charizanis K, Mohan A, et al. Compound loss of muscleblind-like function in myotonic dystrophy. EMBO Mol Med. 2013;5:1887-900 pubmed publisher
    ..While these mutant RNAs inhibit MBNL1 splicing activity in heart and skeletal muscles, Mbnl1 knockout mice fail to recapitulate the full-range of DM ..
  9. Suenaga K, Lee K, Nakamori M, Tatsumi Y, Takahashi M, Fujimura H, et al. Muscleblind-like 1 knockout mice reveal novel splicing defects in the myotonic dystrophy brain. PLoS ONE. 2012;7:e33218 pubmed publisher
    ..In skeletal muscle, nuclear sequestration of the alternative splicing factor muscleblind-like 1 (MBNL1) explains the majority of the alternative splicing defects observed in the HSA(LR) transgenic mouse model which ..
  10. Wang E, Cody N, Jog S, Biancolella M, Wang T, Treacy D, et al. Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins. Cell. 2012;150:710-24 pubmed publisher
    ..events whose regulation depended on Mbnl function in a pattern indicating functional interchangeability between Mbnl1 and Mbnl2...
  11. Han H, Irimia M, Ross P, Sung H, Alipanahi B, David L, et al. MBNL proteins repress ES-cell-specific alternative splicing and reprogramming. Nature. 2013;498:241-5 pubmed publisher
    ..Here we identify the muscleblind-like RNA binding proteins, MBNL1 and MBNL2, as conserved and direct negative regulators of a large program of cassette exon alternative splicing ..
  12. Poulos M, Batra R, Li M, Yuan Y, Zhang C, Darnell R, et al. Progressive impairment of muscle regeneration in muscleblind-like 3 isoform knockout mice. Hum Mol Genet. 2013;22:3547-58 pubmed publisher
    ..While MBNL1 controls fetal-to-adult splicing transitions in muscle and MBNL2 serves a similar role in the brain, the function ..
  13. Osborne R, Lin X, Welle S, Sobczak K, O Rourke J, Swanson M, et al. Transcriptional and post-transcriptional impact of toxic RNA in myotonic dystrophy. Hum Mol Genet. 2009;18:1471-81 pubmed publisher
    ..toxic effects of mutant RNA are mediated partly through sequestration of splicing regulator Muscleblind-like 1 (Mbnl1), a protein that binds to CUG(exp) RNA...
  14. Kanadia R, Shin J, Yuan Y, Beattie S, Wheeler T, Thornton C, et al. Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse poly(CUG) model for myotonic dystrophy. Proc Natl Acad Sci U S A. 2006;103:11748-53 pubmed
    ..Here, we show that overexpression of Mbnl1 in vivo mediated by transduction of skeletal muscle with a recombinant adeno-associated viral vector rescues ..
  15. Terenzi F, Ladd A. Conserved developmental alternative splicing of muscleblind-like (MBNL) transcripts regulates MBNL localization and activity. RNA Biol. 2010;7:43-55 pubmed
    Muscleblind-like (MBNL) proteins have been shown to regulate pre-mRNA alternative splicing, and MBNL1 has been implicated in regulating fetal-to-adult transitions in alternative splicing in the heart...
  16. Yuan Y, Compton S, Sobczak K, Stenberg M, Thornton C, Griffith J, et al. Muscleblind-like 1 interacts with RNA hairpins in splicing target and pathogenic RNAs. Nucleic Acids Res. 2007;35:5474-86 pubmed
    ..have a higher affinity for these pathogenic RNAs versus their normal splicing targets, we demonstrate that MBNL1 possesses comparably high affinities for (CUG)n and (CAG)n RNAs as well as a splicing target, Tnnt3...
  17. Chamberlain C, Ranum L. Mouse model of muscleblind-like 1 overexpression: skeletal muscle effects and therapeutic promise. Hum Mol Genet. 2012;21:4645-54 pubmed publisher
    ..Because MBNL1 loss is thought to play an important role in disease and localized AAV delivery of MBNL1 partially rescues ..
  18. Wheeler T, Lueck J, Swanson M, Dirksen R, Thornton C. Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy. J Clin Invest. 2007;117:3952-7 pubmed
  19. Tang Z, Yarotskyy V, Wei L, Sobczak K, Nakamori M, Eichinger K, et al. Muscle weakness in myotonic dystrophy associated with misregulated splicing and altered gating of Ca(V)1.1 calcium channel. Hum Mol Genet. 2012;21:1312-24 pubmed publisher
    ..Two splicing factors previously implicated in DM1, MBNL1 and CUGBP1, participated in the regulation of E29 splicing. In muscle fibers of wild-type mice, the Ca(V)1...
  20. Miller J, Urbinati C, Teng Umnuay P, Stenberg M, Byrne B, Thornton C, et al. Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. EMBO J. 2000;19:4439-48 pubmed
    ..We propose that DM1 disease is caused by aberrant recruitment of the EXP proteins to the DMPK transcript (CUG)(n) expansion. ..
  21. Brinegar A, Xia Z, Loehr J, Li W, Rodney G, Cooper T. Extensive alternative splicing transitions during postnatal skeletal muscle development are required for calcium handling functions. elife. 2017;6: pubmed publisher
    ..The results demonstrate a previously unknown specificity of calcineurin isoforms as well as the broader impact of alternative splicing during muscle postnatal development. ..
  22. Chou C, Chang P, Wei Y, Lee K. Optical Mapping Approaches on Muscleblind-Like Compound Knockout Mice for Understanding Mechanistic Insights Into Ventricular Arrhythmias in Myotonic Dystrophy. J Am Heart Assoc. 2017;6: pubmed publisher
    ..Control wild-type (Mbnl1+/+; Mbnl2+/+ ) and DM mutant (Mbnl1-/-; Mbnl2+/- ) mice ..
  23. Dixon D, Choi J, El Ghazali A, Park S, Roos K, Jordan M, et al. Loss of muscleblind-like 1 results in cardiac pathology and persistence of embryonic splice isoforms. Sci Rep. 2015;5:9042 pubmed publisher
    ..Deletion of muscleblind-like 1 (Mbnl1(ΔE2/ΔE2)) in 129 sv mice results in QRS, QTc widening, bundle block and STc narrowing at 2-4 months ..
  24. Gladman J, Mandal M, Srinivasan V, Mahadevan M. Age of onset of RNA toxicity influences phenotypic severity: evidence from an inducible mouse model of myotonic dystrophy (DM1). PLoS ONE. 2013;8:e72907 pubmed publisher
    ..mRNA into ribonuclear foci and sequestration of interacting RNA-binding proteins (such as muscleblind-like 1 (MBNL1))...
  25. Lee J, Bennett C, Cooper T. RNase H-mediated degradation of toxic RNA in myotonic dystrophy type 1. Proc Natl Acad Sci U S A. 2012;109:4221-6 pubmed publisher
    ..The CUG transcripts aggregate in the nucleus to form RNA foci and lead to nuclear depletion of Muscleblind-like 1 (MBNL1) and stabilized expression of CUGBP Elav like family 1 (CELF1), both of which are splicing regulatory proteins...
  26. Gladman J, Yadava R, Mandal M, Yu Q, Kim Y, Mahadevan M. NKX2-5, a modifier of skeletal muscle pathology due to RNA toxicity. Hum Mol Genet. 2015;24:251-64 pubmed publisher
    ..Using mouse models of Nkx2-5 over-expression and depletion, we find that NKX2-5 levels modify disease phenotypes in mice with RNA toxicity. ..
  27. Konieczny P, Stepniak Konieczna E, Taylor K, Sznajder L, Sobczak K. Autoregulation of MBNL1 function by exon 1 exclusion from MBNL1 transcript. Nucleic Acids Res. 2017;45:1760-1775 pubmed publisher
    ..Deep sequencing of RNA molecules cross-linked to immunoprecipitated protein particles (CLIP-seq) revealed that MBNL1 binds to MBNL1 exon 1 (e1) encoding both the major part of 5?UTR and an amino-terminal region of MBNL1 protein...
  28. Redmond L, Dumur C, Archer K, Haar J, Lloyd J. Identification of erythroid-enriched gene expression in the mouse embryonic yolk sac using microdissected cells. Dev Dyn. 2008;237:436-46 pubmed publisher
    ..These results provide a catalog of genes expressed during primitive erythropoiesis. ..
  29. Thomas J, Sznajder Ł, Bardhi O, Aslam F, Anastasiadis Z, Scotti M, et al. Disrupted prenatal RNA processing and myogenesis in congenital myotonic dystrophy. Genes Dev. 2017;31:1122-1133 pubmed publisher
    ..test this possibility and the contribution of MBNLs to CDM pathogenesis, we generated mouse Mbnl double (Mbnl1; Mbnl2) and triple (Mbnl1; Mbnl2; Mbnl3) muscle-specific knockout models that recapitulate the ..
  30. Querido E, Gallardo F, Beaudoin M, Ménard C, Chartrand P. Stochastic and reversible aggregation of mRNA with expanded CUG-triplet repeats. J Cell Sci. 2011;124:1703-14 pubmed publisher
    ..The splicing factor Mbnl1 colocalized with individual CUG-repeat transcripts and its aggregation with RNA foci displayed the same stochastic ..
  31. Freyermuth F, Rau F, Kokunai Y, Linke T, Sellier C, Nakamori M, et al. Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy. Nat Commun. 2016;7:11067 pubmed publisher
    ..We find that MBNL1 regulates alternative splicing of SCN5A mRNA and that the splicing variant of SCN5A produced in DM presents a ..
  32. Choi J, Personius K, DiFranco M, Dansithong W, Yu C, Srivastava S, et al. Muscleblind-Like 1 and Muscleblind-Like 3 Depletion Synergistically Enhances Myotonia by Altering Clc-1 RNA Translation. EBioMedicine. 2015;2:1034-47 pubmed publisher
    Loss of Muscleblind-like 1 (Mbnl1) is known to alter Clc-1 splicing to result in myotonia...
  33. Kino Y, Washizu C, Oma Y, Onishi H, Nezu Y, Sasagawa N, et al. MBNL and CELF proteins regulate alternative splicing of the skeletal muscle chloride channel CLCN1. Nucleic Acids Res. 2009;37:6477-90 pubmed publisher
    ..Mutation analyses suggested that exon 7A and its flanking region mediate the effect of MBNL1, whereas another distinct region in intron 6 mediates that of CELF4...
  34. Daughters R, Tuttle D, Gao W, Ikeda Y, Moseley M, Ebner T, et al. RNA gain-of-function in spinocerebellar ataxia type 8. PLoS Genet. 2009;5:e1000600 pubmed publisher
    ..a significant role in SCA8: 1) CUG(exp) transcripts accumulate as ribonuclear inclusions that co-localize with MBNL1 in selected neurons in the brain; 2) loss of Mbnl1 enhances motor deficits in SCA8 mice; 3) SCA8 CUG(exp) ..
  35. Ladd A, Stenberg M, Swanson M, Cooper T. Dynamic balance between activation and repression regulates pre-mRNA alternative splicing during heart development. Dev Dyn. 2005;233:783-93 pubmed
    ..In contrast, PTB and MBNL1 are expressed throughout heart development...
  36. Coram R, Stillwagon S, Guggilam A, Jenkins M, Swanson M, Ladd A. Muscleblind-like 1 is required for normal heart valve development in vivo. BMC Dev Biol. 2015;15:36 pubmed publisher
    ..We previously identified the RNA binding protein muscleblind-like 1 (MBNL1) as a negative regulator of TGFβ signaling and EMT in chicken endocardial cushions ex vivo...
  37. Michel L, Huguet Lachon A, Gourdon G. Sense and Antisense DMPK RNA Foci Accumulate in DM1 Tissues during Development. PLoS ONE. 2015;10:e0137620 pubmed publisher
    ..Sense DMPK RNA foci clearly co-localized with MBNL1 and MBNL2 proteins...
  38. Koscianska E, Witkos T, Kozlowska E, Wojciechowska M, Krzyzosiak W. Cooperation meets competition in microRNA-mediated DMPK transcript regulation. Nucleic Acids Res. 2015;43:9500-18 pubmed publisher
  39. Kino Y, Washizu C, Kurosawa M, Oma Y, Hattori N, Ishiura S, et al. Nuclear localization of MBNL1: splicing-mediated autoregulation and repression of repeat-derived aberrant proteins. Hum Mol Genet. 2015;24:740-56 pubmed publisher
    ..diseases caused by repeat expansions such as myotonic dystrophy, the RNA-binding protein muscleblind-like 1 (MBNL1) accumulates in intranuclear inclusions containing mutant repeat RNA...
  40. Davis J, Salomonis N, Ghearing N, Lin S, Kwong J, Mohan A, et al. MBNL1-mediated regulation of differentiation RNAs promotes myofibroblast transformation and the fibrotic response. Nat Commun. 2015;6:10084 pubmed publisher
    ..for genes that control myofibroblast transformation, and identify the RNA-binding protein muscleblind-like1 (MBNL1)...
  41. Taliaferro J, Vidaki M, Oliveira R, Olson S, Zhan L, Saxena T, et al. Distal Alternative Last Exons Localize mRNAs to Neural Projections. Mol Cell. 2016;61:821-33 pubmed publisher
    ..Depletion of Mbnl1 and/or Mbnl2 reduced localization of hundreds of transcripts, implicating Mbnls in localization of mRNAs to ..
  42. Giudice J, Xia Z, Wang E, Scavuzzo M, Ward A, Kalsotra A, et al. Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development. Nat Commun. 2014;5:3603 pubmed publisher
    ..These AS transitions are enriched among targets of two RNA-binding proteins, Celf1 and Mbnl1, which undergo developmentally regulated changes in expression...
  43. Garcia Lopez A, Llamusi B, Orzáez M, Perez Paya E, Artero R. In vivo discovery of a peptide that prevents CUG-RNA hairpin formation and reverses RNA toxicity in myotonic dystrophy models. Proc Natl Acad Sci U S A. 2011;108:11866-71 pubmed publisher
    ..form CUG hairpins that sequester RNA-binding factors into nuclear foci, including Muscleblind-like-1 protein (MBNL1), which regulate alternative splicing and gene expression...
  44. Gao Z, Cooper T. Reexpression of pyruvate kinase M2 in type 1 myofibers correlates with altered glucose metabolism in myotonic dystrophy. Proc Natl Acad Sci U S A. 2013;110:13570-5 pubmed publisher
    ..CUG(exp)) RNA produces a toxic gain of function by disrupting the functions of RNA splicing factors, such as MBNL1 and CELF1, leading to splicing changes associated with clinical abnormalities...