In vivo effects of the Epstein-Barr virus small RNA EBER-1 on protein synthesis and cell growth regulation.
Recent studies have suggested a role for the Epstein-Barr virus-encoded RNA EBER-1 in malignant transformation. EBER-1 inhibits the activity of the protein kinase PKR, an inhibitor of protein synthesis with tumour suppressor properties. In human 293 cells and murine embryonic fibroblasts, transient expression of EBER-1 promoted total protein synthesis and enhanced the expression of cotransfected reporter genes. However reporter gene expression was stimulated equally well in cells from control and PKR knockout mice. NIH 3T3 cells stably expressing EBER-1 exhibited a greatly increased frequency of colony formation in soft agar, and protein synthesis in these cells was relatively resistant to inhibition by the calcium ionophore A23187. Nevertheless clones containing a high concentration of EBER-1 were not invariably tumourigenic. We conclude that EBER-1 can enhance protein synthesis by a PKR-independent mechanism and that, although this RNA may contribute to the oncogenic potential of Epstein-Barr virus, its expression is not always sufficient for malignant transformation.
Laing
Kenneth G
KG
Department of Biochemistry and Immunology, St. George's Hospital Medical School, Cranmer Terrace, London, United Kingdom.
Elia
Androulla
A
Jeffrey
Ian
I
Matys
Volker
V
Tilleray
Vivienne J
VJ
Souberbielle
Bernard
B
Clemens
Michael J
MJ
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000503:physiopathology; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000502:physiology*; D014162:Transfection; D019892:eIF-2 Kinase / Q000378:metabolism
C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral; D019892:eIF-2 Kinase