Mbnl mutant zebrafish RNA-Seq experiments
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE145270 | GEO | 2021/01/12
REPOSITORIES: GEO
Similar Datasets
Project description:mbnl mutant zebrafish RNA-Seq experiments
| PRJNA606583 | ENA
Project description:Myotonic dystrophy (DM) is a multi-systemic disease that severely impacts cardiac and skeletal muscle functions as well as the central nervous system. DM is unusual because it is RNA-mediated disease due to the expression of C(C)UG expansion RNAs that inhibit the activities of the muscleblind-like (MBNL) proteins. In mice, studies using Mbnl1 and Mbnl2 single knockouts have revealed that Mbnl1 plays a predominant role in skeletal and heart muscle alternative splicing regulation while Mbnl2 performs an analogous splicing function in the brain. However, Mbnl single knockout models fail to recapitulate the full-range of adult-onset DM muscle symptoms. Here, we report that Mbnl1; Mbnl2 double knockouts are embryonic lethal while Mbnl1-/-; Mbnl2+/- mice, which express no Mbnl1 and reduced levels of Mbnl2, are viable but develop cardinal features of adult-onset DM cardiac and skeletal muscle disease including reduced lifespan, heart conduction block, severe myotonia and progressive skeletal muscle weakness. Mbnl2 protein levels are elevated in both Mbnl1-/- and Mbnl1-/-; Mbnl2+/- knockouts where Mbnl2 targets Mbnl1-regulated exons. These findings support the MBNL loss-of-function model for DM and provide novel Mbnl compound knockout models to investigate the molecular pathways disrupted by RNA-mediated disease. Mbnl2 protein-RNA interactions were assessed in 4-month-old WT and Mbnl1-/- quadriceps muscles in triplicates by HITS-CLIP.
2013-12-01 | E-GEOD-47794 | biostudies-arrayexpress
Project description:Myotonic dystrophy (DM) is a multi-systemic disease that severely impacts cardiac and skeletal muscle functions as well as the central nervous system. DM is unusual because it is RNA-mediated disease due to the expression of C(C)UG expansion RNAs that inhibit the activities of the muscleblind-like (MBNL) proteins. In mice, studies using Mbnl1 and Mbnl2 single knockouts have revealed that Mbnl1 plays a predominant role in skeletal and heart muscle alternative splicing regulation while Mbnl2 performs an analogous splicing function in the brain. However, Mbnl single knockout models fail to recapitulate the full-range of adult-onset DM muscle symptoms. Here, we report that Mbnl1; Mbnl2 double knockouts are embryonic lethal while Mbnl1-/-; Mbnl2+/- mice, which express no Mbnl1 and reduced levels of Mbnl2, are viable but develop cardinal features of adult-onset DM cardiac and skeletal muscle disease including reduced lifespan, heart conduction block, severe myotonia and progressive skeletal muscle weakness. Mbnl2 protein levels are elevated in both Mbnl1-/- and Mbnl1-/-; Mbnl2+/- knockouts where Mbnl2 targets Mbnl1-regulated exons. These findings support the MBNL loss-of-function model for DM and provide novel Mbnl compound knockout models to investigate the molecular pathways disrupted by RNA-mediated disease.
2013-12-01 | GSE47794 | GEO
Project description:Here, we analyze the RNA-binding preferences of the planarian smed-mbnl-like-2, smed-mbnl-1 (isoform X1), smed-bruli, smed-mbnl-1 (isoform Xins), and smed-mbnl-like-1 protein using RNAcompete.
2016-08-01 | GSE75554 | GEO
Project description:Here, we analyze the RNA-binding preferences of the planarian smed-mbnl-like-2, smed-mbnl-1 (isoform X1), smed-bruli, smed-mbnl-1 (isoform Xins), and smed-mbnl-like-1 protein using RNAcompete. In the RNAcompete assay, a purified GST-tagged protein is incubated with an excess of RNA pool and bound RNA from individual pulldown experiments are directly labeled and hybridized to a custom Agilent 244K microarray.
2016-08-01 | E-GEOD-75554 | biostudies-arrayexpress
Project description:Mapping MBNL-regulated genome-wide alternative polyadenylation: We report that depletion of Mbnl proteins in mouse embryo fibroblasts (MEFs), DM mouse model quadriceps muscle, and DM-autopsy muscle tissue leads to mis-regulation of alternative polyadenylation
2014-09-05 | GSE60487 | GEO
Project description:Alternative splicing has emerged as a fundamental mechanism not only for the diversification of protein isoforms but also for the spatiotemporal control of development. Therefore, a better understanding of how this mechanism is regulated has the potential not only to elucidate fundamental biological principles, but also to decipher pathological mechanisms implicated in diseases where normal splicing networks are misregulated. Here, we took advantage of human pluripotent stem cells to decipher during human myogenesis the role of MBNL proteins, a family of tissue-specific splicing regulators whose loss of function is associated with Myotonic Dystrophy type 1, an inherited neuromuscular disease. Thanks to the CRISPR/Cas9 technology, we generated human-induced pluripotent stem cells (hiPSCs) depleted in MBNL proteins and evaluated the molecular and functional consequences of this loss on the generation of skeletal muscle cells. Our results indicated that MBNL proteins are specifically required for the late myogenic maturation but not for early myogenic commitment. By a transcriptomic analysis, we further demonstrated that MBNL proteins are not only important for the regulation of alternative splicing but also for the regulation of gene expression. Together, our study reveals the temporal requirement of MBNL proteins in human myogenesis and should facilitate the identification of new therapeutic strategies capable to cope the loss of function of these MBNL proteins.
2021-08-04 | GSE161897 | GEO
Project description:Alternative splicing has emerged as a fundamental mechanism not only for the diversification of protein isoforms but also for the spatiotemporal control of development. Therefore, a better understanding of how this mechanism is regulated has the potential not only to elucidate fundamental biological principles, but also to decipher pathological mechanisms implicated in diseases where normal splicing networks are misregulated. Here, we took advantage of human pluripotent stem cells to decipher during human myogenesis the role of MBNL proteins, a family of tissue-specific splicing regulators whose loss of function is associated with Myotonic Dystrophy type 1, an inherited neuromuscular disease. Thanks to the CRISPR/Cas9 technology, we generated human-induced pluripotent stem cells (hiPSCs) depleted in MBNL proteins and evaluated the molecular and functional consequences of this loss on the generation of skeletal muscle cells. Our results indicated that MBNL proteins are specifically required for the late myogenic maturation but not for early myogenic commitment. By a transcriptomic analysis, we further demonstrated that MBNL proteins are not only important for the regulation of alternative splicing but also for the regulation of gene expression. Together, our study reveals the temporal requirement of MBNL proteins in human myogenesis and should facilitate the identification of new therapeutic strategies capable to cope the loss of function of these MBNL proteins.
2021-08-04 | GSE161029 | GEO
Project description:Bekaert2012 - Reconstruction of D.rerio Metabolic Network
Danio rerio
metabolic model accounting for subcellular compartmentalisation (ZebraGEM)
This SBML representation of the D. rerio
(zebrafish) metabolic network is made available under the Creative Commons Attribution-Share Alike 3.0 Unported Licence (see www.creativecommons.org
).
This model is described in the article:
Reconstruction of Danio rerio Metabolic Model Accounting for Subcellular Compartmentalisation.
Bekaert M.
PLoS One. 2012;7(11):e49903.
Abstract:
Plant and microbial metabolic engineering is commonly used in the production of functional foods and quality trait improvement. Computational model-based approaches have been used in this important endeavour. However, to date, fish metabolic models have only been scarcely and partially developed, in marked contrast to their prominent success in metabolic engineering. In this study we present the reconstruction of fully compartmentalised models of the Danio rerio (zebrafish) on a global scale. This reconstruction involves extraction of known biochemical reactions in D. rerio for both primary and secondary metabolism and the implementation of methods for determining subcellular localisation and assignment of enzymes. The reconstructed model (ZebraGEM) is amenable for constraint-based modelling analysis, and accounts for 4,988 genes coding for 2,406 gene-associated reactions and only 418 non-gene-associated reactions. A set of computational validations (i.e., simulations of known metabolic functionalities and experimental data) strongly testifies to the predictive ability of the model. Overall, the reconstructed model is expected to lay down the foundations for computational-based rational design of fish metabolic engineering in aquaculture.
This model is hosted on BioModels Database
and identified by: MODEL1204120000
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. PMID: 20587024
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to [CC0 Public Domain Dedication>http://creativecommons.org/publicdomain/zero/1.0/] for more information.
2005-01-01 | MODEL1204120000 | BioModels
Project description:Differentially expressed genes in myotubes derived from MBNL knockouts hiPSCs generated by CRISPR/Cas9.
| PRJNA679805 | ENA