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Mus musculus

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

PROVIDER: PRJNA262627 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1593020_1.fastq.gz	Fastqsanger.gz
	SRR1593020_2.fastq.gz	Fastqsanger.gz
	SRR1593021_1.fastq.gz	Fastqsanger.gz
	SRR1593021_2.fastq.gz	Fastqsanger.gz
	SRR1593012_1.fastq.gz	Fastqsanger.gz

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Project description:Functional Antagonism Between CELF and Mbnl Proteins in Cytoplasm and Nucleus [hearts]

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Project description:Conserved functional antagonism between CELF and MBNL proteins regulates stem cell-specific alternative splicing and regeneration in planarians (dataset 1)

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Project description:Conserved functional antagonism between CELF and MBNL proteins regulates stem cell-specific alternative splicing and regeneration in planarians (dataset 3)

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Transcriptome-wide Regulation of Splicing and mRNA Localization by Muscleblind Proteins

Project description:The Muscleblind-like (Mbnl) family of RNA-binding proteins plays important roles in muscle and eye development and in Myotonic Dystrophy (DM), where expanded CUG or CCUG repeats functionally deplete Mbnl proteins. We identified transcriptome-wide functional and biophysical targets of Mbnl proteins in brain, heart, muscle, and myoblasts using RNA sequencing and crosslinking/immunoprecipitation-sequencing approaches. This analysis identified several hundred splicing events whose regulation depended on Mbnl function, in a pattern indicative of functional interchangeability between Mbnl1 and Mbnl2. A nucleotide resolution RNA map associated repression or activation of exon splicing with Mbnl binding near either 3' splice site or near the downstream 5' splice site, respectively. Transcriptomic analysis of sub-cellular compartments uncovered a global role for Mbnls in regulating localization of mRNAs encoding membrane, synaptic and other proteins in both mouse and Drosophila cells, and Mbnls also contribute to protein secretion. These findings hold several new implications for DM pathogenesis. To assess global functions of Muscleblind proteins, RNA-Seq was performed using WT and Mbnl1 KO brain, heart, and muscle (5 mice each). Additionally, C2C12 mouse myoblasts were depleted of Mbnl1, Mbnl2, or both. Subcellular fractionation experiments were performed to analyze mRNA localization following depletion of Mbnl1 and Mbnl2 in C2C12 mouse myoblasts, and following depletion of Mbnl in Drosophila S-2R+ cells. CLIP-Seq was also performed against Mbnl1 in mouse brain, heart, muscle, and C2C12 myoblasts. Finally, ribosome footprinting was performed with C2C12 mouse myoblasts that were depleted of Mbnl1, Mbnl2, or both.

2012-08-17 | E-GEOD-39911 | biostudies-arrayexpress

Transcriptome-wide Regulation of Splicing and mRNA Localization by Muscleblind Proteins

2012-08-17 | GSE39911 | GEO

Conserved functional antagonism between CELF and MBNL proteins regulates stem cell-specific alternative splicing and regeneration in planarians

Project description:Understanding gene regulation in stem cells is key to understanding stem cell biology.Contrary to transcriptional regulation the function of alternative splicing (AS) in stem cells is poorly understood. Here we study function and mechanisms of AS in a powerful in vivo model for stem cell biology, the planarian S. mediterranea. Knockdown of AS factors, computational analyses of massive RNA-sequencing data, phenotyping, and biochemical binding assays revealed a stem cell specific AS program comprising hundreds of alternative exons, intron retention events, and microexons. The conserved AS factors CELF/MBNL are main regulators of this program. We show that they antagonize each other by directly promoting or repressing stem cell specific AS events. Knockdown of CELF/MBNL leads to defective regeneration by affecting self-renewal and differentiation, respectively. Thus, AS is of key importance for stem cell regulation in vivo and antagonistic regulation by CELF/MBNL is likely an ancestral feature of animal stem cells. Sequencing of polyA-selected RNA from Schmidtea mediterranea individuals after control, smed-bruno-like(RNAi) and mbnl(RNAi) after 20,25,30 days after RNAi

2016-08-01 | E-GEOD-75296 | biostudies-arrayexpress

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