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RBM10 Modulates Apoptosis and Influences TNF-? Gene Expression.

ABSTRACT: Recent evidence suggests that protein encoded by the RNA Binding Motif 10 (RBM10) gene has the ability to modulate apoptosis. The objective of this study was to test this hypothesis by manipulating RBM10 expression levels and examining the downstream consequences. The results showed that transient overexpression of RBM10 correlated with significantly elevated levels of tumour necrosis factor alpha (TNF-?) mRNA and soluble TNF-? (sTNF-?) protein, and increased apoptosis (phosphatidyl serine exposure on the outer cell membrane and nuclear condensation). Stable RNA interference-mediated RBM10 knockdown clones were less susceptible to TNF-?-mediated apoptosis, and had decreased sTNF-? protein levels. Elevated levels of TNF-? associated with RBM10 overexpression resulted from increased TNF-? transcription, not TNF-? mRNA stabilization. These results suggest that RBM10 has the ability to modulate apoptosis, and that it does so via a mechanism involving alterations to TNFR super family-mediated signaling. These data provide the first direct evidence that human RBM10 can function as an apoptosis modulator and cytokine expression regulator.

SUBMITTER: Wang K

PROVIDER: S-EPMC4583097 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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RBM10 Modulates Apoptosis and Influences TNF-α Gene Expression.

Wang Ke K Bacon Mackensey L ML Tessier Julie J JJ Rintala-Maki Nina D ND Tang Vanessa V Sutherland Leslie C LC

Journal of cell death 20120127

Recent evidence suggests that protein encoded by the RNA Binding Motif 10 (RBM10) gene has the ability to modulate apoptosis. The objective of this study was to test this hypothesis by manipulating RBM10 expression levels and examining the downstream consequences. The results showed that transient overexpression of RBM10 correlated with significantly elevated levels of tumour necrosis factor alpha (TNF-α) mRNA and soluble TNF-α (sTNF-α) protein, and increased apoptosis (phosphatidyl serine expos ...[more]

PMID: 26446321

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Project description:BackgroundSchistosoma mansoni is the major causative agent of schistosomiasis. The parasite takes advantage of host signals to complete its development in the human body. Tumor necrosis factor-alpha (TNF-alpha) is a human cytokine involved in skin inflammatory responses, and although its effect on the adult parasite's metabolism and egg-laying process has been previously described, a comprehensive assessment of the TNF-alpha pathway and its downstream molecular effects is lacking.Methodology/principal findingsIn the present work we describe a possible TNF-alpha receptor (TNFR) homolog gene in S. mansoni (SmTNFR). SmTNFR encodes a complete receptor sequence composed of 599 amino acids, and contains four cysteine-rich domains as described for TNFR members. Real-time RT-PCR experiments revealed that SmTNFR highest expression level is in cercariae, 3.5 (+/-0.7) times higher than in adult worms. Downstream members of the known human TNF-alpha pathway were identified by an in silico analysis, revealing a possible TNF-alpha signaling pathway in the parasite. In order to simulate parasite's exposure to human cytokine during penetration of the skin, schistosomula were exposed to human TNF-alpha just 3 h after cercariae-to-schistosomula in vitro transformation, and large-scale gene expression measurements were performed with microarrays. A total of 548 genes with significantly altered expression were detected, when compared to control parasites. In addition, treatment of adult worms with TNF-alpha caused a significantly altered expression of 1857 genes. Interestingly, the set of genes altered in adults is different from that of schistosomula, with 58 genes in common, representing 3% of altered genes in adults and 11% in 3 h-old early schistosomula.Conclusions/significanceWe describe the possible molecular elements and targets involved in human TNF-alpha effect on S. mansoni, highlighting the mechanism by which recently transformed schistosomula may sense and respond to this host mediator at the site of cercarial penetration into the skin.

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RBM10 Modulates Apoptosis and Influences TNF-? Gene Expression.

Publications

RBM10 Modulates Apoptosis and Influences TNF-α Gene Expression.

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