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A Ribonucleoprotein Complex Protects the Interleukin-6 mRNA from Degradation by Distinct Herpesviral Endonucleases


During replication of Kaposi’s sarcoma-associated herpesvirus (KSHV), the vast majority of mRNAs in the cytoplasm are cleaved and degraded by the viral nuclease SOX. However, some mRNAs escape this fate, including the transcript encoding the immunoregulatory cytokine IL-6. Here, we discover that this escape is mediated by a group of proteins that associates with a sequence element on the IL-6 mRNA. One of these proteins is nucleolin (NCL), a factor with diverse roles in RNA processing that is frequently co-opted during viral infection. During KSHV replication, a proportion of NCL is redirected from the nucleolar subcompartment of the nucleus into the cytoplasm, where it binds both the IL-6 3’ UTR and a complex of cellular proteins including the translation initiation factor eIF4H. This network of interactions is required for escape from virus-induced degradation. Collectively, these findings reveal novel interplay between the SOX escapees and the cellular mRNA stabilization machinery, and shed light on the complex crosstalk between viruses and hosts over the control of gene expression.


Vyšlo v časopise: A Ribonucleoprotein Complex Protects the Interleukin-6 mRNA from Degradation by Distinct Herpesviral Endonucleases. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004899
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004899

Souhrn

During replication of Kaposi’s sarcoma-associated herpesvirus (KSHV), the vast majority of mRNAs in the cytoplasm are cleaved and degraded by the viral nuclease SOX. However, some mRNAs escape this fate, including the transcript encoding the immunoregulatory cytokine IL-6. Here, we discover that this escape is mediated by a group of proteins that associates with a sequence element on the IL-6 mRNA. One of these proteins is nucleolin (NCL), a factor with diverse roles in RNA processing that is frequently co-opted during viral infection. During KSHV replication, a proportion of NCL is redirected from the nucleolar subcompartment of the nucleus into the cytoplasm, where it binds both the IL-6 3’ UTR and a complex of cellular proteins including the translation initiation factor eIF4H. This network of interactions is required for escape from virus-induced degradation. Collectively, these findings reveal novel interplay between the SOX escapees and the cellular mRNA stabilization machinery, and shed light on the complex crosstalk between viruses and hosts over the control of gene expression.


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