WRN modulates translation by influencing nuclear mRNA export in HeLa cancer cells

WRN 通过影响 HeLa 癌细胞中的核 mRNA 输出来调节翻译

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作者:Juan Manuel Iglesias-Pedraz, Diego Matia Fossatti-Jara, Valeria Valle-Riestra-Felice, Sergio Rafael Cruz-Visalaya, Jose Antonio Ayala Felix, Lucio Comai

Background

The Werner syndrome protein (WRN) belongs to the RecQ family of helicases and its loss of function

Conclusions

Our findings suggest that WRN influences the export of mRNAs from the nucleus through its interaction with the NXF1 export receptor thereby affecting cellular proteostasis. In summary, we identified a new partner and a novel function of WRN, which is especially important for the proliferation of cancer cells.

Results

To identify the mechanism underlying this metabolic shift, we examined global protein synthesis and mRNA nucleocytoplasmic distribution after WRN knockdown. We determined that WRN depletion in HeLa cells attenuates global protein synthesis without affecting the level of key components of the mRNA export machinery. We further observed that WRN depletion affects the nuclear export of mRNAs and demonstrated that WRN interacts with mRNA and the Nuclear RNA Export Factor 1 (NXF1). Conclusions: Our findings suggest that WRN influences the export of mRNAs from the nucleus through its interaction with the NXF1 export receptor thereby affecting cellular proteostasis. In summary, we identified a new partner and a novel function of WRN, which is especially important for the proliferation of cancer cells.

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