Dephosphorylation of HuR protein during alphavirus infection is associated with HuR relocalization to the cytoplasm
Autor(es): Dickson Alexa M, Anderson John R, Barnhart Michael D, Sokoloski Kevin J, Oko Lauren, Opyrchal Mateusz, Galanis Evanthia, Wilusz Carol J, Morrison Thomas E, Wilusz Jeffrey
Resumo: We have demonstrated previously that the cellular HuR protein binds U-rich elements in the 3' untranslated region (UTR) of Sindbis virus RNA - relocalizes from the nucleus to the cytoplasm upon Sindbis virus infection in 293T cells. In this study, we show that two alphaviruses, Ross River virus - Chikungunya virus, lack the conserved high-affinity U-rich HuR binding element in their 3' UTRs but still maintain the ability to interact with HuR with nanomolar affinities through alternative binding elements. The relocalization of HuR protein occurs during Sindbis infection of multiple mammalian cell types as well as during infections with three other alphaviruses. Interestingly, the relocalization of HuR is not a general cellular reaction to viral infection, as HuR protein remained largely nuclear during infections with dengue - measles virus. Relocalization of HuR in a Sindbis infection required viral gene expression, was independent of the presence of a high-affinity U-rich HuR binding site in the 3' UTR of the virus, - was associated with an alteration in the phosphorylation state of HuR. Sindbis virus-induced HuR relocalization was mechanistically distinct from the movement of HuR observed during a cellular stress response, as there was no accumulation of caspase-mediated HuR cleavage products. Collectively, these data indicate that virus-induced HuR relocalization to the cytoplasm is specific to alphavirus infections - is associated with distinct posttranslational modifications of this RNA-binding protein.
Palavras-Chave: Nuclear transport; RNA binding protein; RNA Turnover; RNA viruses; Virology; Alphavirus; Nuclear-cytoplasmic shuttling
Imprenta: The Journal of Biological Chemistry, v. 287, n. 43, p. 36229-36238, 2012
Identificador do objeto digital: 10.1074/jbc.M112.371203
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Genome ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Protein synthesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Dengue ; Chikungunya virus - Immunology
Data de publicação: 2012
