IRES-mediated Translation of Cellular Messenger RNA Operates in eIF2α- independent Manner during Stress

IRES-mediated Translation of Cellular Messenger RNA Operates in eIF2α- independent Manner during Stress

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dc.contributor.author Thakor, Nehal
dc.contributor.author Holcik, Martin
dc.date.accessioned 2012-04-18T19:32:15Z
dc.date.available 2012-04-18T19:32:15Z
dc.date.created 2011 en_US
dc.date.issued 2012-04-18
dc.identifier Nucleic Acids Research 2011, 1-12. en_US
dc.identifier.other 10.1093/nar/gkr701 en_US
dc.identifier.uri http://hdl.handle.net/10393/22744
dc.description.abstract Physiological and pathophysiological stress attenuates global translation via phosphorylation of eIF2α. This in turn leads to the reprogramming of gene expression that is required for adaptive stress response. One class of cellular messenger RNAs whose translation was reported to be insensitive to eIF2α phosphorylation-mediated repression of translation is that harboring an Internal Ribosome Entry Site (IRES). IRES-mediated translation of several apoptosis-regulating genes increases in response to hypoxia, serum deprivation or gamma irradiation and promotes tumor cell survival and chemoresistance. However, the molecular mechanism that allows IRES-mediated translation to continue in an eIF2α-independent manner is not known. Here we have used the X-chromosome linked Inhibitor of Apoptosis, XIAP, IRES to address this question. Using toeprinting assay, western blot analysis and polysomal profiling we show that the XIAP IRES supports cap-independent translation when eIF2α is phosphorylated both in vitro and in vivo. During normal growth condition eIF2α-dependent translation on the IRES is preferred. However, IRES-mediated translation switches to eIF5B-dependent mode when eIF2α is phosphorylated as a consequence of cellular stress. en_US
dc.language.iso en en_US
dc.title IRES-mediated Translation of Cellular Messenger RNA Operates in eIF2α- independent Manner during Stress en_US
dc.type Article en_US

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