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Loss of microRNA-targets in the 3'-untranslated region as a mechanism of retroviral insertional activation of Growth Factor Independence 1

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  • Magdalena Julia Dabrowska, Denmark
  • Karen Dybkær, Denmark
  • Hans Erik Johnsen, Denmark
  • Bruce Wang, Denmark
  • Matthias Wabl, Denmark
  • Finn Skou Pedersen
  • Hæmatologisk Afdeling, Aalborg Sygehus
  • Department of Molecular Biology
The non-oncogene bearing retrovirus SL3-3 murine leukemia virus induces strictly T-cell lymphomas with a mean latency of 2-4 months in mice of the NMRI-inbred (i) strain. By high throughput sequencing of retroviral tags, we have identified the genomic region encoding 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 1kb window of the 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 in 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.
Original languageEnglish
JournalJournal of Virology
Volume83
Issue16
Pages (from-to)8051-8061
Number of pages11
ISSN0022-538X
DOIs
Publication statusPublished - 2009

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