Activation of c-myb by 5' retrovirus promoter insertion in myeloid neoplasms is dependent upon an intact alternative splice donor site (SD') in gag.
Alternative splicing in Mo-MuLV recruits a splice donor site, SD', within the gag that is required for optimal replication in vitro. Remarkably, this SD' site was also found to be utilized for production of oncogenic gag-myb fusion RNA in 100% of murine-induced myeloid leukemia (MML) in pristane-treated BALB/c mice. Therefore, we investigated the influence of silent mutations of SD' in this model. Although there was no decrease in the overall incidence of disease, there was a decrease in the incidence of myeloid leukemia with a concomitant increase in lymphoid leukemia. Importantly, there was a complete lack of myeloid tumors associated with 5' insertional mutagenic activation of c-myb, suggesting the specific requirement of the SD' site in this mechanism.
Ramirez
Jean Marie
JM
Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS UMR5121, UMI, IFR122, Montpellier, France.
Houzet
Laurent
L
Koller
Richard
R
Bies
Juraj
J
Wolff
Linda
L
Mougel
Marylène
M
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D004195:Disease Models, Animal; D015870:Gene Expression; D020570:Genes, myb; D007945:Leukemia, Lymphoid / Q000473:pathology / Q000821:virology; D007951:Leukemia, Myeloid / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000473:pathology; D016662:Virus Integration
D012333:RNA, Messenger; D012367:RNA, Viral