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In Vitro and In Vivo Modulation of Alternative Splicing by the Biguanide Metformin.

ABSTRACT: In Vitro and In Vivo Modulation of Alternative Splicing by the Biguanide Metformin.

PROVIDER: PRJNA577137 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10269700_1.fastq.gz	Fastqsanger.gz
	SRR10269700_2.fastq.gz	Fastqsanger.gz
	SRR10269701_1.fastq.gz	Fastqsanger.gz
	SRR10269701_2.fastq.gz	Fastqsanger.gz
	SRR10269702_1.fastq.gz	Fastqsanger.gz

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In Vitro and In Vivo Modulation of Alternative Splicing by the Biguanide Metformin.

Project description:Major physiological changes are governed by alternative splicing of RNA, and its misregulation may lead to specific diseases. With the use of a genome-wide approach, we show here that this splicing step can be modified by medication and demonstrate the effects of the biguanide metformin, on alternative splicing. The mechanism of action involves AMPK activation and downregulation of the RBM3 RNA-binding protein. The effects of metformin treatment were tested on myotonic dystrophy type I (DM1), a multisystemic disease considered to be a spliceopathy. We show that this drug promotes a corrective effect on several splicing defects associated with DM1 in derivatives of human embryonic stem cells carrying the causal mutation of DM1 as well as in primary myoblasts derived from patients. The biological effects of metformin were shown to be compatible with typical therapeutic dosages in a clinical investigation involving diabetic patients. The drug appears to act as a modifier of alternative splicing of a subset of genes and may therefore have novel therapeutic potential for many more diseases besides those directly linked to defective alternative splicing.

2019-10-12 | GSE138789 | GEO

In Vitro and In Vivo Modulation of Alternative Splicing by the Biguanide Metformin.

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Modulation of insulin secretion through RBFOX2-mediated alternative splicing

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Regulation of alternative splicing by histone modifications

Project description:Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. Here, we demonstrate a direct role for histone modifications in alternative splicing. We find distinctive histone modification signatures which correlate with splicing outcome in a set of human genes. Modulation of histone modifications causes splice site switching. The mechanism for histone-mediated splice site selection involves a histone mark which is read by a chromatin protein, which in turn recruits a splicing regulator. These results outline an adaptor system for reading of histone marks by the pre-mRNA splicing machinery. To obtain an estimate of how many PTB-dependent alternative splicing events are regulated by SET2/MRG15-mediated recruitment of PTB, we carried out a genomewide comparative analysis of alternative splicing in hMSC cells depleted of either SETD2, MRG15 or PTB using specific siRNAs, or mock-depleted using a control siRNA.

2010-02-10 | E-GEOD-19373 | biostudies-arrayexpress

Transcriptome analysis of alternative splicing events regulated by SRSF10 reveals position-dependent splicing modulation.

Project description:Splicing factor SRSF10 is known to function as a sequence-specific splicing activator. Here, we used RNA-seq coupled with bioinformatics analysis to identify the extensive splicing network regulated by SRSF10 in chicken cells. We found that SRSF10 promoted both exon inclusion and exclusion. Functionally, many of SRSF10-verified alternative exons are linked to pathways of stress and apoptosis. Importantly, reconstituted SRSF10 in knockout cells recovered wild-type splicing patterns and considerably rescued the stress-related defects. Together, our results provide mechanistic insight into SRSF10-regulated alternative splicing events in vivo and demonstrate that SRSF10 plays a crucial role in cell survival under stress conditions. RNA-seq for wide type (WT) and SRSF10-deficient (KO) chicken DT40 cells

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Modulation of insulin secretion through RBFOX2-mediated alternative splicing [RNA-seq MIN6]

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Project description:Modulation of insulin secretion through RBFOX2-mediated alternative splicing [eCLIP-Seq MIN6]

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Regulation of alternative splicing by histone modifications

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Transcriptome analysis of alternative splicing events regulated by SRSF10 reveals position-dependent splicing modulation.

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Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB

Project description:This SuperSeries is composed of the following subset Series: GSE23513: Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB (HJAY) GSE23514: Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB (Exon array) Refer to individual Series

2010-09-01 | E-GEOD-23522 | biostudies-arrayexpress

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