SRSF10 Regulates Alternative Splicing and Is Required for Adipocyte Differentiation

Huang, Li; Cheng, Yuanming; Wu, Wenwu; Liu, Yuguo; Wei, Ning; Feng, Xiaoyan; Xie, Zhiqin; Feng, Ying

doi:10.1128/mcb.01674-13

Cited by 54 publications

(58 citation statements)

References 28 publications

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“…Specific to adipogenesis, differential promoter usage and alternative splicing are required for the expression of the canonical adipogenic transcription factor Ppar␥ (26 -28, 43). Other regulatory factors are also formed from alternative splicing, including nCOR1 and Lipin1 (33,43,44). In the present study, we identified distinct roles of each splicing factor in generating Pparg mRNA splice variants.…”

Section: Determining Adipogenic Factors In the 14-3-3 Interactomementioning

confidence: 50%

“…The spliceosome is responsible for constitutive and alternative splicing of mRNA, whereby intronic regions of mRNA are removed or sections of mRNA enriched with splicing factors at regulatory elements are removed, respectively (24). Various splicing factors have been found to be important for adipogenesis (33,34), but no studies have directly tested the role of the spliceosome in this process. To this end, we found that inhibition of the spliceosome with madrasin was sufficient to block 3T3-L1 adipogenesis and prevent the generation of various Pparg splice variants.…”

Section: Determining Adipogenic Factors In the 14-3-3 Interactomementioning

confidence: 99%

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Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA-splicing factors during adipogenesis

Mugabo

Sadeghi

Fang

et al. 2018

Journal of Biological Chemistry

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Adipogenesis involves a complex signaling network requiring strict temporal and spatial organization of effector molecules. Molecular scaffolds, such as 14-3-3 proteins, facilitate such organization, and we have previously identified 14-3-3ζ as an essential scaffold in adipocyte differentiation. The interactome of 14-3-3ζ is large and diverse, and it is possible that novel adipogenic factors may be present within it, but this possibility has not yet been tested. Herein, we generated mouse embryonic fibroblasts from mice overexpressing a tandem affinity purification (TAP) epitope-tagged 14-3-3ζ molecule. After inducing adipogenesis, TAP-14-3-3ζ complexes were purified, followed by MS analysis to determine the 14-3-3ζ interactome. We observed more than 100 proteins that were unique to adipocyte differentiation, 56 of which were novel interacting partners. Among these, we were able to identify previously established regulators of adipogenesis ( Ptrf/Cavin1) within the 14-3-3ζ interactome, confirming the utility of this approach to detect adipogenic factors. We found that proteins related to RNA metabolism, processing, and splicing were enriched in the interactome. Analysis of transcriptomic data revealed that 14-3-3ζ depletion in 3T3-L1 cells affected alternative splicing of mRNA during adipocyte differentiation. siRNA-mediated depletion of RNA-splicing factors within the 14-3-3ζ interactome, that is, of Hnrpf, Hnrpk, Ddx6, and Sfpq, revealed that they have essential roles in adipogenesis and in the alternative splicing of and the adipogenesis-associated gene In summary, we have identified novel adipogenic factors within the 14-3-3ζ interactome. Further characterization of additional proteins within the 14-3-3ζ interactome may help identify novel targets to block obesity-associated expansion of adipose tissues.

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Section: Determining Adipogenic Factors In the 14-3-3 Interactomementioning

confidence: 50%

Section: Determining Adipogenic Factors In the 14-3-3 Interactomementioning

confidence: 99%

Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA-splicing factors during adipogenesis

Mugabo

Sadeghi

Fang

et al. 2018

Journal of Biological Chemistry

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“…However, cross-linking immunoprecipitation-sequencing (CLiP-seq) data in HEK293 cells (Sanford et al, 2009) revealed a binding site for SRSF1 (alias ASF/SF2) in exon 6 of PPARG ( Figure S3A). Therefore, according to the models proposed for the exclusion of exon 11 in MST1R gene (alias RON) mediated by SRSF1 (Ghigna et al, 2005) and exon 7 in Lipin1a mediated by SRSF10 (Li et al, 2014), the binding of SRSF1 to PPARG exon 6 might contribute to exon 5 exclusion. RNA immunoprecipitation (RIP) in control HEK293 cells, as well as in cells overexpressing SRSF1, confirmed that this splicing factor binds to PPARG pre-mRNA and mature transcripts ( Figures 1D and S3B).…”

Section: Pparg Activation Increases Exon 5 Skipping With the Contribumentioning

confidence: 99%

PPARγΔ5, a Naturally Occurring Dominant-Negative Splice Isoform, Impairs PPARγ Function and Adipocyte Differentiation

et al. 2018

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“…Specific to adipogenesis, differential promoter usage and alternative splicing are required for the expression of the canonical adipogenic transcription factor Pparγ (51)(52)(53). Other regulatory factors are also formed from alternative splicing, including nCOR1 and Lipin1 (54,55). Future studies are required to determine whether 14-3-3ζ directly binds to these splicing factors and how it regulates their splicing activity to generate essential adipogenic factors.…”

Section: Discussionmentioning

confidence: 99%

Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA splicing factors during adipogenesis

Mugabo

Sadeghi

Fang

et al. 2017

Preprint

View full text Add to dashboard Cite

Adipogenesis is facilitated by a complex signaling network requiring strict temporal and spatial organization of effector molecules. Molecular scaffolds, such as 14-3-3 proteins, coordinate such events, and we have previously identified 14-3-3ζ as an essential scaffold in adipocyte differentiation. The interactome of 14-3-3ζ is large and diverse, and it is possible that novel adipogenic factors may be present within it. Mouse embryonic fibroblasts from mice over-expressing a TAP-epitope-tagged 14-3-3ζ molecule were generated, and following the induction of adipogenesis, TAP-14-3-3ζ complexes were purified, followed by mass spectrometry analysis to determine the 14-3-3ζ interactome. Over 100 proteins were identified as being unique to adipocyte differentiation, of which 56 were novel interacting partners. Previously established regulators of adipogenesis (ie, Ptrf/Cavin1 and Phb2) were found within the 14-3-3ζ interactome, confirming the ability of this approach to identify regulators of adipocyte differentiation. An enrichment of proteins in the interactome related to RNA metabolism, processing, and splicing was identified, and analysis of transcriptomic data revealed that 14-3-3ζ depletion in 3T3-L1 cells affected the alternative splicing of mRNA during adipocyte differentiation. Of the RNA splicing factors within the 14-3-3ζ interactome, depletion of Hnrnpf, Hnrnpk, Ddx6, and Sfpq by siRNA revealed essential roles of these proteins in adipogenesis and their roles in the alternative splicing of Lpin1. In summary, novel adipogenic factors can be detected within the 14-3-3ζ interactome, and further characterization of additional proteins within the 14-3-3ζ interactome has the potential of identifying novel targets to block the expansion of adipose tissue mass that occurs in obesity.

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SRSF10 Regulates Alternative Splicing and Is Required for Adipocyte Differentiation

Cited by 54 publications

References 28 publications

Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA-splicing factors during adipogenesis

Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA-splicing factors during adipogenesis

PPARγΔ5, a Naturally Occurring Dominant-Negative Splice Isoform, Impairs PPARγ Function and Adipocyte Differentiation

Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA splicing factors during adipogenesis

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