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Journal of Virology, August 2009, p. 8051-8061, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00427-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Loss of MicroRNA Targets in the 3' Untranslated Region as a Mechanism of Retroviral Insertional Activation of Growth Factor Independence 1{triangledown}

Magdalena Julia Dabrowska,1,2 Karen Dybkaer,1,2 Hans Erik Johnsen,1 Bruce Wang,3 Matthias Wabl,4 and Finn Skou Pedersen2*

Department of Haematology, Aalborg Hospital, Aarhus University Hospital, Aarhus, Denmark,1 Department of Molecular Biology, Aarhus University, Aarhus, Denmark,2 Picobella L.L.C., 863 Mitten Road, Suite 101, Burlingame, California 94010,3 Department of Microbiology and Immunology, University of California, San Francisco, California 941434

Received 27 February 2009/ Accepted 20 May 2009

The non-oncogene-bearing retrovirus SL3-3 murine leukemia virus induces strictly T-cell lymphomas with a mean latency of 2 to 4 months in mice of the NMRI-inbred (NMRI-i) strain. By high-throughput sequencing of retroviral tags, we have identified the genomic region carrying the transcriptional repressor and oncogene growth factor independence 1 (Gfi1) as a frequent target for SL3-3 in the NMRI-i mouse genome. Twenty-four SL3-3 insertions were identified within a 1-kb window of the 3' untranslated region (3'UTR) of the Gfi1 gene, a clustering pattern unique for this lymphoma model. Expression analysis determined that the Gfi1 gene was transcriptionally activated by SL3-3 insertions, and an upregulation of Gfi1 protein expression was detected for tumors harboring insertions in the Gfi1 3'UTR. Here we provide data in support of a mechanism by which retroviral insertions in the Gfi1 3'UTR decouple microRNA-mediated posttranscriptional regulation.

* Corresponding author. Mailing address: Department of Molecular Biology, Aarhus University, C.F. Møllers Allé, Bldg. 1130, DK-8000 Aarhus C, Denmark. Phone: 4589422614. Fax: 4586196500. E-mail: fsp{at}mb.au.dk

{triangledown} Published ahead of print on 27 May 2009.

Journal of Virology, August 2009, p. 8051-8061, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00427-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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