Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

SRSF10 regulates alternative splicing and is required for adipocyte differentiation.

ABSTRACT: During adipocyte differentiation, significant alternative splicing changes occur in association with the adipogenic process. However, little is known about roles played by splicing factors in this process. We observed that mice deficient for the splicing factor SRSF10 exhibit severely impaired development of subcutaneous white adipose tissue as a result of defects in adipogenic differentiation. To identify splicing events responsible for this, RNA-seq analysis was performed using embryonic fibroblast cells. Several SRSF10-affected splicing events that are implicated in adipogenesis have been identified. Skipping of lipin1 exon 7 is controlled by SRSF10-regulated cis-element located in the constitutive exon 8. The activity of this element depends on the binding of SRSF10 and correlates with the relative abundance of lipin1a mRNA. A series of experiments demonstrated that SRSF10 controls the production of lipin1a and thus promotes adipocyte differentiation. Indeed, lipin1a expression could rescue SRSF10-mediated adipogenic defects. Taken together, our results identify SRSF10 as an essential regulator for adipocyte differentiation and also provide new insights into splicing control by SRSF10 in lipin1 pre-mRNA splicing. RNA-seq for wide type (WT) and SRSF10-deficient (KO) mouse MEF cells

ORGANISM(S): Mus musculus

SUBMITTER: Ying Feng

PROVIDER: E-GEOD-54226 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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SRSF10 regulates alternative splicing and is required for adipocyte differentiation.

Li Huang H Cheng Yuanming Y Wu Wenwu W Liu Yuguo Y Wei Ning N Feng Xiaoyan X Xie Zhiqin Z Feng Ying Y

Molecular and cellular biology 20140407 12

During adipocyte differentiation, significant alternative splicing changes occur in association with the adipogenic process. However, little is known about roles played by splicing factors in this process. We observed that mice deficient for the splicing factor SRSF10 exhibit severely impaired development of subcutaneous white adipose tissue (WAT) as a result of defects in adipogenic differentiation. To identify splicing events responsible for this, transcriptome sequencing (RNA-seq) analysis wa ...[more]

PMID: 24710272

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Project description:Alternative RNA splicing analysis in Hep3B cell cultured under 21% (N1,3,5) or 1.2% (H2,4,6) oxygen Hypoxia is a common characteristic of many solid tumors. The hypoxic microenvironment stabilizes hypoxia-inducible transcription factor 1? (HIF1?) and 2? (HIF2?) to activate gene transcription, which promotes tumor cell survival. 95% of human genes are alternatively spliced, producing RNA isoforms that code functionally distinct proteins. Thus, effective hypoxia response requires increased HIF target gene transcription as well as proper RNA splicing of these HIF target genes. However, it is unclear if and how hypoxia regulates RNA splicing of HIF target genes. This study determined the effects of hypoxia on alternative splicing (AS) of HIF and non-HIF target genes in Hep3B cells and characterized the role of HIF in regulating AS of HIF induced genes. The results indicated that hypoxia generally promotes exon inclusion for hypoxia-induced, but reduces exon inclusion for hypoxia reduced genes. Mechanistically, HIF activity, but not hypoxia per se is found to be necessary and sufficient to increase exon inclusion of several HIF target genes including pyruvate dehydrogenase kinase 1 (PDK1). PDK1 splicing reporters confirmed that transcriptional activation by HIF is sufficient to increase exon inclusion of PDK1 splicing reporter. In contrast, transcriptional activation of the PDK1 minigene by other transcription factor in the absence of endogenous HIF target gene activation fails to alter PDK1 RNA splicing, demonstrating a novel role of HIF target gene(s) in regulating RNA splicing of HIF target genes. Implications:This study demonstrates a novel function of HIF in regulating RNA splicing of HIF target genes. We analyzed total RNA from Hep3B cells cultured under 21% (N1,3,5) or 1.2% (H2,4,6) oxygen using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by Altanalyze software version 2.0.7. Techinical replicates were performed for Nx and Hx treated Hep3B cells

Dataset Information

SRSF10 regulates alternative splicing and is required for adipocyte differentiation.

Publications

SRSF10 regulates alternative splicing and is required for adipocyte differentiation.

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