Cytoplasmic relocalization of heterogeneous nuclear ribonucleoprotein A1 controls translation initiation of specific mRNAs.
Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is a nucleocytoplasmic shuttling protein that regulates gene expression through its action on mRNA metabolism and translation. The cytoplasmic redistribution of hnRNP A1 is a regulated process during viral infection and cellular stress. Here, we show that hnRNP A1 is an internal ribosome entry site (IRES) trans-acting factor that binds specifically to the 5' untranslated region of both the human rhinovirus-2 and the human apoptotic peptidase activating factor 1 (apaf-1) mRNAs, thereby regulating their translation. Furthermore, the cytoplasmic redistribution of hnRNP A1 after rhinovirus infection leads to enhanced rhinovirus IRES-mediated translation, whereas the cytoplasmic relocalization of hnRNP A1 after UVC irradiation limits the UVC-triggered translational activation of the apaf-1 IRES. Therefore, this study provides a direct demonstration that IRESs behave as translational enhancer elements regulated by specific trans-acting mRNA binding proteins in given physiological conditions. Our data highlight a new way to regulate protein synthesis in eukaryotes through the subcellular relocalization of a nuclear mRNA-binding protein.
Cammas
Anne
A
Institut National de la Santé et de la Recherche Médicale U563, Toulouse, F-31000, France.
Pileur
Frédéric
F
Bonnal
Sophie
S
Lewis
Stephen M
SM
Lévêque
Nicolas
N
Holcik
Martin
M
Vagner
Stéphan
S
D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics* / Q000528:radiation effects; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012229:Rhinovirus / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism
D053477:Apoptotic Protease-Activating Factor 1; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C000619656:hnRNPA1 protein, human