0000000000374879

AUTHOR

Jack Puymirat

showing 3 related works from this author

rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences

2018

Myotonic dystrophy type 1 and type 2 (DM1, DM2) are caused by expansions of CTG and CCTG repeats, respectively. RNAs containing expanded CUG or CCUG repeats interfere with the metabolism of other RNAs through titration of the Muscleblind-like (MBNL) RNA binding proteins. DM2 follows a more favorable clinical course than DM1, suggesting that specific modifiers may modulate DM severity. Here, we report that the rbFOX1 RNA binding protein binds to expanded CCUG RNA repeats, but not to expanded CUG RNA repeats. Interestingly, rbFOX1 competes with MBNL1 for binding to CCUG expanded repeats and overexpression of rbFOX1 partly releases MBNL1 from sequestration within CCUG RNA foci in DM2 muscle ce…

0301 basic medicineModels MolecularProtein Conformation alpha-Helical[SDV]Life Sciences [q-bio]General Physics and AstronomyGene ExpressionRNA-binding proteinCrystallography X-Raychemistry.chemical_compoundMOLECULAR-BASISGene expressionMBNL1Myotonic DystrophyComputingMilieux_MISCELLANEOUSMultidisciplinaryCHLORIDE CHANNELQRNA-Binding ProteinsRecombinant Proteins3. Good healthCell biologyCONGENITAL HEART-DISEASEDrosophila melanogasterThermodynamicsSKELETAL-MUSCLERNA Splicing FactorsCUG REPEATSProtein BindingRNA Splicing Factorsmusculoskeletal diseasesSTEADY-STATEcongenital hereditary and neonatal diseases and abnormalitiesScienceRBFOX1BiologyMyotonic dystrophyBinding CompetitiveGeneral Biochemistry Genetics and Molecular BiologyArticle03 medical and health sciencesmedicineEscherichia coliAnimalsHumansProtein Interaction Domains and MotifsBinding siteNucleotide MotifsMuscle SkeletalSPLICING REGULATOR RBFOX2MUSCLEBLIND PROTEINSBinding SitesPRE-MESSENGER-RNARNAGeneral Chemistrymedicine.diseaseDisease Models AnimalKinetics030104 developmental biologychemistryTRIPLET REPEATRNAProtein Conformation beta-Strand3111 Biomedicine
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Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional …

2016

International audience; BACKGROUND: Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity, challenging both medical management and clinical trials. The CTG expansion size is the main factor determining the age of onset although no factor can finely predict phenotype and prognosis. Differences between males and females have not been specifically reported. Our aim is to study gender impact on DM1 phenotype and severity.METHODS: We first performed cross-sectional analysis of main multiorgan clinical parameters in 1409 adult DM1 patients (\textgreater18y) from the DM-Scope nationwide registry and obser…

Male0301 basic medicineDatabases FactualPhysiologyCross-sectional studyMyotonic dystrophylcsh:MedicineDiseasecomputer.software_genreinfo:eu-repo/classification/mesh/Socioeconomic FactorsLaryngologyinfo:eu-repo/classification/mesh/Myotonic Dystrophy/epidemiology*0302 clinical medicineMedicine and Health SciencesEthnicitiesMedicineinfo:eu-repo/classification/mesh/FemaleFrench Peoplelcsh:Scienceinfo:eu-repo/classification/mesh/Adulteducation.field_of_studyMultidisciplinaryinfo:eu-repo/classification/mesh/Factual*Death ratesDatabaseCognitive NeurologyMortality rateDysphagia3. Good healthPhenotypeCognitive impairmentNeurologyPhysiological ParametersFemaleinfo:eu-repo/classification/mesh/Databasesinfo:eu-repo/classification/mesh/MaleResearch ArticleAdultMaternal inheritanceCognitive NeurosciencePopulation[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human geneticsMyotonic dystrophy03 medical and health sciencesPopulation MetricsAdultsHumansObesitySex DistributioneducationDemographyinfo:eu-repo/classification/mesh/Cross-Sectional StudiesPopulation BiologyCataractsbusiness.industrylcsh:RBody WeightBiology and Life Sciencesmedicine.diseaseMyotoniaThyroid disorderinfo:eu-repo/classification/mesh/Sex DistributionHealth CareOphthalmologyCross-Sectional Studies030104 developmental biologyOtorhinolaryngologySocioeconomic Factors[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human geneticsAge Groups[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologieLens DisordersPeople and Placesinfo:eu-repo/classification/mesh/Myotonic Dystrophy/mortalityCognitive Sciencelcsh:QPopulation Groupings[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologieHealth StatisticsMorbidityAge of onsetbusinessinfo:eu-repo/classification/mesh/Phenotype*computerinfo:eu-repo/classification/mesh/Humans030217 neurology & neurosurgeryNeurosciencePLOS ONE
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Towards development of a statistical framework to evaluate myotonic dystrophy type 1 mRNA biomarkers in the context of a clinical trial

2020

AbstractMyotonic dystrophy type 1 (DM1) is a rare genetic disorder, characterised by muscular dystrophy, myotonia, and other symptoms. DM1 is caused by the expansion of a CTG repeat in the 3’-untranslated region of DMPK. Longer CTG expansions are associated with greater symptom severity and earlier age at onset. The primary mechanism of pathogenesis is thought to be mediated by a gain of function of the CUG-containing RNA, that leads to trans-dysregulation of RNA metabolism of many other genes. Specifically, the alternative splicing (AS) and alternative polyadenylation (APA) of many genes is known to be disrupted. In the context of clinical trials of emerging DM1 treatments, it is important…

0301 basic medicineMicroarrayPhysiologyMicroarraysBioinformaticsBiochemistryMachine Learning0302 clinical medicineMathematical and Statistical TechniquesMedicine and Health SciencesMyotonic DystrophyMuscular dystrophyOligonucleotide Array Sequence AnalysisClinical Trials as TopicMultidisciplinaryMusclesQStatisticsRGenetic disorderMuscle AnalysisBody FluidsNucleic acidsBloodBioassays and Physiological AnalysisTreatment OutcomeGenetic DiseasesPhysical SciencesMedicineRegression AnalysisAnatomyDatabases Nucleic AcidResearch Articlemusculoskeletal diseasesGenetic Markerscongenital hereditary and neonatal diseases and abnormalitiesScienceContext (language use)Linear Regression AnalysisBiostatisticsResearch and Analysis MethodsPolyadenylationMyotonic dystrophyMyotonin-Protein Kinase03 medical and health sciencesmedicineGeneticsHumansRNA MessengerStatistical MethodsLeast-Squares AnalysisGeneClinical GeneticsModels Geneticbusiness.industryAlternative splicingBiology and Life Sciencesmedicine.diseaseMyotoniaAlternative Splicing030104 developmental biologyRNA processingRNAGene expressionbusinessTrinucleotide repeat expansionTrinucleotide Repeat Expansion030217 neurology & neurosurgeryBiomarkersMathematicsForecastingPLoS ONE
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