MANUEL IGLESIAS-PEDRAZ, Juan, Diego Matia Antonio FOSSATTI JARA, Valeria VALLE-RIESTRA-FELICE, Sergio RAFAEL CRUZ-VISALAYA, Jose Antonio Ayala FELIX and Lucio COMAI. WRN modulates translation by influencing nuclear mRNA export in HeLa cancer cells. BMC Molecular and Cell Biology. London: BMC, 2020, vol. 21, No 1, p. 1-16. ISSN 2661-8850. Available from: https://dx.doi.org/10.1186/s12860-020-00315-9.
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Basic information
Original name WRN modulates translation by influencing nuclear mRNA export in HeLa cancer cells
Authors MANUEL IGLESIAS-PEDRAZ, Juan, Diego Matia Antonio FOSSATTI JARA (604 Peru, guarantor, belonging to the institution), Valeria VALLE-RIESTRA-FELICE, Sergio RAFAEL CRUZ-VISALAYA, Jose Antonio Ayala FELIX and Lucio COMAI.
Edition BMC Molecular and Cell Biology, London, BMC, 2020, 2661-8850.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10601 Cell biology
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 2.033
RIV identification code RIV/00216224:14310/20:00117233
Organization unit Faculty of Science
Doi http://dx.doi.org/10.1186/s12860-020-00315-9
UT WoS 000578331300001
Keywords in English Werner syndrome protein; mRNA export; NXF1 export receptor; Translation; Cancer; Senescence
Tags rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Marie Šípková, DiS., učo 437722. Changed: 4/12/2020 11:44.
Abstract
Background The Werner syndrome protein (WRN) belongs to the RecQ family of helicases and its loss of function results in the premature aging disease Werner syndrome (WS). We previously demonstrated that an early cellular change induced by WRN depletion is a posttranscriptional decrease in the levels of enzymes involved in metabolic pathways that control macromolecular synthesis and protect from oxidative stress. This metabolic shift is tolerated by normal cells but causes mitochondria dysfunction and acute oxidative stress in rapidly growing cancer cells, thereby suppressing their proliferation. 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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