Loss of MicroRNA targets in the 3' untranslated region as a mechanism of retroviral insertional activation of growth factor independence 1.
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.
Dabrowska
Magdalena Julia
MJ
Department of Haematology, Aalborg Hospital, Aarhus University Hospital, Denmark.
Dybkaer
Karen
K
Johnsen
Hans Erik
HE
Wang
Bruce
B
Wabl
Matthias
M
Pedersen
Finn Skou
FS
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D012326:RNA Splicing; D012192:Retroviridae Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation; D016662:Virus Integration
D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D035683:MicroRNAs; D014157:Transcription Factors