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Alternative splicing regulation by homologous Muscleblind proteins

ABSTRACT: We provide data showing alternative splicing regulation by Muscleblind proteins in MEFs. MEFs lacking functional Muscleblind (DKO MEFs) were stably reconstituted with Muscleblind proteins from Homo sapiens, Ciona intestinalis, Drosophila melanogaster, Caenorhabditis elegans or Trichoplax adhaerens and splicing regulation was explored using RNA-seq analysis followed by MISO (Mixture of Isoforms).

ORGANISM(S): Mus musculus

PROVIDER: GSE79095 | GEO | 2016/06/01

SECONDARY ACCESSION(S): PRJNA314940

REPOSITORIES: GEO

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Alternative splicing regulation by homologous Muscleblind proteins

Project description:We provide data showing alternative splicing regulation by Muscleblind proteins in MEFs. MEFs lacking functional Muscleblind (DKO MEFs) were stably reconstituted with Muscleblind proteins from Homo sapiens, Ciona intestinalis, Drosophila melanogaster, Caenorhabditis elegans or Trichoplax adhaerens and splicing regulation was explored using RNA-seq analysis followed by MISO (Mixture of Isoforms). Alternative splicing was accessed using RNA-sequencing data from five DKO MEF lines reconstituted with different GFP-tagged Muscleblind homologs or GFP alone and compared to RNA-seq data from three WT MEF lines and three control DKO MEFs (no Muscleblind reconstitution). A total of 12 samples were used for high-throughput sequencing.

2016-06-01 | E-GEOD-79095 | biostudies-arrayexpress

MBL-1/Muscleblind regulates neuronal differentiation and controls the splicing of a terminal selector in Caenorhabditis elegans

Project description:The muscleblind family of mRNA splicing regulators is conserved across species and regulate the development of muscles and the nervous system. However, how Muscleblind proteins regulate neuronal fate specification and neurite morphogenesis at the single-neuron level is not well understood. In this study, we found that the C. elegans Muscleblind/MBL-1 promotes axonal growth in the touch receptor neurons (TRNs) by regulating microtubule stability and polarity. Transcriptomic analysis identified dozens of MBL-1-controlled splicing events in genes related to neuronal differentiation or microtubule functions. Among the MBL- 1 targets, the LIM-domain transcription factor mec-3 is the terminal selector for the TRN fate and induces the expression of many TRN terminal differentiation genes. MBL-1 promotes the splicing of the mec-3 long isoform, which are essential for TRN fate specification, and inhibits the short isoforms that have much weaker activities in activating downstream genes. MBL-1 promotes mec-3 splicing through three “YGCU(U/G)Y” motifs located downstream of the included exon, which is similar to the mechanisms used by mammalian Muscleblind and suggests a deeply conserved context-dependency of the splicing regulation. Interestingly, the expression of mbl-1 in the TRNs is dependent on the mec-3 long isoform, indicating a positive feedback loop between the splicing regulator and the terminal selector. Finally, through a forward genetic screen, we found that MBL-1 promotes neurite growth partly by inhibiting the DLK-1/p38 MAPK pathway. In summary, our study provides mechanistic understanding of the role of Muscleblind in regulating cell fate specification and neuronal morphogenesis.

2024-08-14 | GSE274472 | GEO

Muscleblind Splicing Factor Regulates Longevity Through p38 MAPK Signaling

Project description:Muscleblind-like splicing regulators (MBNLs) are RNA-binding factors that have an important role in developmental processes. Dysfunction of these factors is a key contributor of different neuromuscular degenerative disorders, including Myotonic Dystrophy type 1 (DM1). Since DM1 is a multisystemic disease characterized by symptoms resembling accelerated aging, we asked which cellular processes do MBNLs regulate that make them necessary for normal lifespan. By utilizing the model organism Caenorhabditis elegans, we found that loss of MBL-1 (the sole ortholog of mammalian MBNLs), which is known to be required for normal lifespan, shortens lifespan by decreasing the activity of p38 MAPK/PMK-1 as well as the function of transcription factors ATF-7 and SKN-1. Furthermore, we show that mitochondrial stress caused by knockdown of mitochondrial electron transport chain components promotes the longevity of mbl-1 mutants in a partially PMK-1-dependent manner. Together, the data establish a mechanism of how DM1-associated loss of muscleblind affects lifespan. Furthermore, this study suggests that mitochondrial stress could alleviate symptoms caused by the dysfunction of muscleblind splicing factor, creating a potential approach to investigate for therapy.

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small RNA sequencing of two developmental stages of Ciona intestinalis

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2010-03-27 | E-GEOD-21078 | biostudies-arrayexpress

Gene expression of ovary and neural complex in adult Ciona intestinalis

Project description:To compare with new Ciona intestinalis microarray NimbleGen 135k, we peformed gene expression analysis of GPL14686. Total RNAs from common samples with a part of NimbleGen's analysis are used for this analysis. Ovary and Neural Complex from adult Ciona intestinalis, duplicate, 2 time points during spawning

2011-11-05 | E-GEOD-33498 | biostudies-arrayexpress

Muscleblind Splicing Factor Regulates Longevity Through p38 MAPK Signaling

Project description:Muscleblind Splicing Factor Regulates Longevity Through p38 MAPK Signaling

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Project description:The transcriptome of unfertilized eggs of Ciona intestinalis was determined with microarrays.

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Transcriptome analysis of Ciona intestinalis to identify genes expressed in the adult organs.

Project description:Among urochordates (tunicates)âthe closest living relatives of vertebratesâCiona intestinalis is increasingly being used as a model organism in the field of developmental biology. Ciona intestinalis is the seventh animal which genome published; the ~120-Mbp euchromatin region is estimated to contain ~16,000 protein-coding genes. In addition, analyses of more than one million ESTs have provided the foundation for gene models and associated transcriptomes. The fertilized Ciona intestinalis egg develops into a tadpole larva with a simplified chordate body plan, and then it metamorphose into adult sea squirt of sessile filter feeder. One of interests in the field of developmental biology is to understand what kind of genes are expressed in the body and how spatially and/or temporally coordinated expression of genes is controlled. In this study, we investigated the entire gene expression of 11 organs of adult Ciona; the neural complex, branchial sac, esophagus, stomach, endostyle, intestine, body-wall muscle, heart, blood cells, ovary, and testis. Our data would provides basic information of transcriptome in each organ and help to understand gene expression control of organ specific genes. Gene expressions in 11 organs of adult Ciona intestinalis; blood cells, branchial sac, digestive grand, endostyle, esophagus, heart, body-wall muscle, neural complex, ovary, stomach and testis. Three independent experiments were performed at each tissue using different individuals for each experiment.

2010-10-27 | E-GEOD-24941 | biostudies-arrayexpress

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