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Functional Antagonism Between CELF and Mbnl Proteins in Cytoplasm and Nucleus [CLIP-seq]

ABSTRACT: The CUG-BP and ETR-3-like factor 1 (Celf1) RNA binding protein plays an important role in heart and muscle development, and is over-expressed in the disease myotonic dystrophy. Celf1 has known roles in regulation of RNA splicing, RNA stability, and protein translation. To identify transcriptome-wide targets of the Celf1 protein, we performed CLIP-seq against Celf1 using the 3B1 antibody, in myoblasts, heart tissue, and muscle tissue.

ORGANISM(S): Mus musculus

PROVIDER: GSE61892 | GEO | 2014/12/01

SECONDARY ACCESSION(S): PRJNA262628

REPOSITORIES: GEO

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Functional Antagonism Between CELF and Mbnl Proteins in Cytoplasm and Nucleus [muscle]

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Project description:The CUG-BP and ETR-3-like factor 1 (Celf1) RNA binding protein plays an important role in heart and muscle development, and is over-expressed in the disease myotonic dystrophy. Celf1 has known roles in regulation of RNA splicing, RNA stability, and protein translation. To identify transcriptome-wide targets of the Celf1 protein in heart, we performed RNA-Seq of polyA+ RNA from mice inducibly expressing Celf1 in the heart. Mice were engineered to express the reverse tetracycline trans-activator (rtTA) from a heart-specific alpha myosin heavy chain promoter, and an N-terminal Flag-tagged version of the LYLQ isoform of human Celf1 from a tet-inducible promoter. Mice were fed doxycycline to induce Celf1 expression in heart, and hearts were harvested from 3 mice each at 12 hour, 24 hour, 72 hour, and 7 day time points. To account for potential doxycycline-dependent effects, control mice were fed doxycycline for 72 hours but these mice did not contain the tet-inducible Celf1 cassette. In total, 15 hearts were analyzed by RNA-Seq.

2014-04-01 | E-GEOD-56185 | biostudies-arrayexpress

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Project description:Muscles undergo developmental transitions in gene expression and alternative splicing that are necessary to refine sarcomere structure and contractility. CUG-BP and ETR-3-like (CELF) family RNA binding proteins are important regulators of RNA processing during myogenesis that are misregulated in diseases such as myotonic dystrophy (DM1). In this work we report a function for Bruno 1 (Bru1, Arrest), a CELF1/2 family homolog in Drosophila, during early muscle myogenesis as well as during later stages of sarcomere assembly and myofiber maturation. We identify an imbalance in growth in sarcomere length and width during later stages of development as the mechanism driving abnormal radial growth, myofibril fusion and the formation of hollow myofibrils in bru1 mutant muscle. Molecularly, we characterize a genome-wide transition from immature to mature sarcomere gene isoform expression in flight muscle development that is blocked in bru1 mutants. We performed whole proteome mass spectrometry in control and bru1 mutant muscle to identify changes to the proteome, and correlated these changes to gene expression and exon use gleaned from mRNA-Seq. Our results reveal the conserved nature of CELF function in regulating cytoskeletal dynamics in muscle development, and demonstrate that defective RNA processing due to misexpression of CELF proteins causes wide-reaching structural defects and progressive malfunction of affected muscles that cannot be rescued by late-stage gene replacement.

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Ares Swanson MBNL mutant study

Project description:MBNL1 is a known splicing factor and is related to Myotonic Dystrophy (DM). This study examines the tissue specific splicing patterns of MBNL1 using a mutant and wild type mouse across three tissues (heart,brain,quadricep) related publications: Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy. Du H, etal Nat Struct Mol Biol. 2010 Feb;17(2):187-93. and Hum Mol Genet. 2006 Jul 1;15(13):2087-97. Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy. Lin X, Miller JW, Mankodi A, Kanadia RN, Yuan Y, Moxley RT, Swanson MS, Thornton CA. We examined quadricep,heart and brain of a mouse MBNL1 mutant to test whether MBNL mutants creates a tissue specific splicing defect. These samples were compared to the tissues of a wild type mouse.

2012-07-30 | E-GEOD-28640 | biostudies-arrayexpress

Functional Antagonism Between CELF and Mbnl Proteins in Cytoplasm and Nucleus

Project description:This SuperSeries is composed of the SubSeries listed below.

2014-12-01 | GSE61893 | GEO

Myotonic dystrophy type 1 (DM1) leads to altered mRNA expression in heart tissue

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