A new player in oncogenesis: AUF1/hnRNPD overexpression leads to tumorigenesis in transgenic mice.
AUF1/heterogeneous nuclear ribonucleoprotein D (hnRNPD) binds to adenylate uridylate-rich elements contained in the 3' untranslated region of many short-lived mRNAs. This binding has been shown in vitro to control the stability of adenylate uridylate-rich element-containing mRNAs, including mRNAs encoding proto-oncogenes, cytokines, or other signaling molecules. However, no studies have yet been undertaken to identify the mRNAs subject to AUF1-mediated regulation in vivo. The purpose of our study was to investigate the biological functions of AUF1. Thus, we derived transgenic (Tg) mice, which overexpress one isoform of AUF1, the p37(AUF1). Mice of the three Tg lines analyzed exhibit altered levels of expression of several target mRNAs, such as c-myc, c-jun, c-fos, granulocyte macrophage colony-stimulating factor, and tumor necrosis factor alpha. The Tg line with the highest amount of Tg p37(AUF1) protein developed sarcomas. The tumors strongly expressed AUF1 Tg protein and Cyclin D1. Taken together, our data show that: (a) AUF1 is a key regulatory factor of gene expression in vivo; and (b) the deregulation of this heterogeneous nuclear ribonucleoprotein leads to tumorigenesis.
Gouble
Agnàs
A
Centre de Biologie du Développement, CNRS-UMR5547, Université Paul Sabatier, Bâtiment 4R3, 31062 Toulouse, Cedex 4, France.
Grazide
Solàne
S
Meggetto
Fabienne
F
Mercier
Pascale
P
Delsol
Georges
G
Morello
Dominique
D
D000199:Actins / Q000235:genetics; D000818:Animals; D019938:Cyclin D1 / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000235:genetics*; D012513:Sarcoma, Experimental / Q000209:etiology*
D000199:Actins; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D019938:Cyclin D1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor