Pumilio directs deadenylation-associated translational repression of the cyclin-dependent kinase 1 activator RGC-32
| Autor: | Michele Brocard, Sarika Khasnis, Claire Shannon-Lowe, Michelle J. West, C. David Wood |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Herpesvirus 4 Human Polyadenylation genetic structures QP0551 Muscle Proteins Cell Cycle Proteins Nerve Tissue Proteins Biology RNA Prot Comp 03 medical and health sciences Cell Line Tumor CDC2 Protein Kinase Genetics medicine Humans Psychological repression 3' Untranslated Regions B cell QR355 QP0620 Messenger RNA Cyclin-dependent kinase 1 B-Lymphocytes MRNA cleavage Cell Cycle RNA-Binding Proteins RNA 3' Polyadenylation Signals Cell cycle Burkitt Lymphoma eye diseases QR 3. Good health Cell biology Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Protein Biosynthesis QH0605 sense organs Poly A Cytokinesis Protein Binding Transcription Factors |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Response gene to complement-32 (RGC-32) activates cyclin-dependent kinase 1, regulates the cell cycle and is deregulated in many human tumours. We previously showed that RGC-32 expression is upregulated by the cancer-associated Epstein-Barr virus (EBV) in latently infected B cells through the relief of translational repression. We now show that EBV infection of naïve primary B cells also induces RGC-32 protein translation. In EBV-immortalised cell lines, we found that RGC-32 depletion resulted in cell death, indicating a key role in B cell survival. Studying RGC-32 translational control in EBV-infected cells, we found that the RGC-32 3′untranslated region (3′UTR) mediates translational repression. Repression was dependent on a single Pumilio binding element (PBE) adjacent to the polyadenylation signal. Mutation of this PBE did not affect mRNA cleavage, but resulted in increased polyA tail length. Consistent with Pumilio-dependent recruitment of deadenylases, we found that depletion of Pumilio in EBV-infected cells increased RGC-32 protein expression and polyA tail length. The extent of Pumilio binding to the endogenous RGC-32 mRNA in EBV-infected cell lines also correlated with RGC-32 protein expression. Our data demonstrate the importance of RGC-32 for the survival of EBV-immortalised B cells and identify Pumilio as a key regulator of RGC-32 translation. |
| Databáze: | OpenAIRE |
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