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Pumilio directs deadenylation-associated translational repression of the cyclin-dependent kinase 1 activator RGC-32

journal contribution
posted on 2023-06-09, 11:49 authored by Michèle Brocard, Sarika Khasnis, David WoodDavid Wood, Claire Shannon-Lowe, Michelle WestMichelle West
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.

Funding

Elucidating the regulation and function of the cell-cycle regulator RGC-32 in Epstein-Barr virus transformed cells; G1149; MRC-MEDICAL RESEARCH COUNCIL; MR/K01952X/\

History

Publication status

  • Published

File Version

  • Published version

Journal

Nucleic Acids Research

ISSN

0305-1048

Publisher

Oxford University Press

Issue

7

Volume

46

Page range

3707-3725

Department affiliated with

  • Biochemistry Publications

Research groups affiliated with

  • Haematology Research Group Publications
  • Gene Expression Research Group Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-01-30

First Open Access (FOA) Date

2018-01-30

First Compliant Deposit (FCD) Date

2018-01-29

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