Viral-mediated stabilization of AU-rich element containing mRNA contributes to cell transformation

T Kuroshima; M Aoyagi; M Yasuda; T Kitamura; J P Jehung; M Ishikawa; Y Kitagawa; Y Totsuka; M Shindoh; F Higashino

doi:10.1038/onc.2011.14

Viral-mediated stabilization of AU-rich element containing mRNA contributes to cell transformation

Oncogene. 2011 Jun 30;30(26):2912-20. doi: 10.1038/onc.2011.14. Epub 2011 Feb 14.

Authors

T Kuroshima¹, M Aoyagi, M Yasuda, T Kitamura, J P Jehung, M Ishikawa, Y Kitagawa, Y Totsuka, M Shindoh, F Higashino

Affiliation

¹ Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan.

PMID: 21317928
DOI: 10.1038/onc.2011.14

Abstract

E4orf6 is one of the oncogene products of adenovirus, and it also has an important role for transportation of cellular and viral messenger RNA (mRNA) during the late phase of virus infection. We previously revealed that E4orf6 controls the fate of AU-rich element (ARE) containing mRNA by perturbing the chromosome maintenance region 1-dependent export mechanism. Here, we show that E4orf6 stabilizes ARE-mRNA through the region required for its oncogenic activity and ubiquitin E3 ligase assembly. Cells that failed to stabilize ARE-mRNA after HuR knockdown were unable to produce colonies in soft agar, even when E4orf6 was expressed. Furthermore, the stabilized ARE-mRNA induced the transformation of rodent immortalized cells. These findings indicate that stabilized ARE-mRNA is necessary, if not all, for the oncogenic activity of E4orf6 and has the potential to transform cells, at least under a certain condition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenoviridae / physiology*
Adenoviridae Infections / complications
Adenoviridae Infections / genetics
Adenovirus E4 Proteins / chemistry
Adenovirus E4 Proteins / metabolism
Adenovirus E4 Proteins / physiology
Animals
Base Composition / genetics
Base Composition / physiology
Cell Transformation, Neoplastic / genetics*
Cell Transformation, Neoplastic / metabolism
Cells, Cultured
Cytoplasm / metabolism
Humans
Intracellular Signaling Peptides and Proteins / metabolism
Nuclear Proteins
Protein Binding
Protein Interaction Domains and Motifs / physiology
Protein Structure, Secondary / physiology
Protein Transport / genetics
Protein Transport / physiology
RNA Stability / genetics
RNA Stability / physiology*
RNA, Messenger / genetics
RNA, Messenger / metabolism*
RNA-Binding Proteins
Rats
Regulatory Elements, Transcriptional / genetics

Substances

ANP32A protein, human
Adenovirus E4 Proteins
E4orf6 protein, adenovirus
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
RNA, Messenger
RNA-Binding Proteins