The existence of a putative regulatory element in 3′-untranslated region of proto-oncogene HOX11's mRNA

Abstract

HOX11 encodes a homeodomain-containing transcription factor which directs the development of the spleen during embryogenesis. While HOX11 expression is normally silenced through an unknown mechanism in all tissues by adulthood, the deregulation of HOX11 expression is associated with leukemia, such as T-cell acute lymphoblastic leukemia. The elucidation of regulatory elements contributing to the molecular mechanism underlying the regulation of HOX11 gene expression is of great importance. Previous reports of HOX11 regulatory elements mainly focused on the 5′-flanking region of HOX11 on the chromosome related to transcriptional control. To expand the search of putative ds-elements involved in HOX11 regulation at the post-transcriptional level, we analyzed HOX11 mRNA 3′-untranslated region (3′UTR) and found an AU-rich region. To characterize this AU-rich region, in vitro analysis of HOX11 mRNA 3′UTR was performed with human RNA-binding protein HuR, which interacts with AU-rich element (ARE) existing in the 3′UTR of many growth factors' and cytokines' mRNAs. Our results showed that the HOX11 mRNA 3′UTR can specifically bind with human HuR protein in vitro. This specific binding could be competed effectively by typical ARE containing RNA. After the deletion of the AU-rich region present in the HOX11 mRNA 3′UTR, the interaction of HOX11 mRNA 3′UTR with HuR protein was abolished. These findings suggest that HOX11 mRNA 3′UTR contains cis-acting element which shares similarity in the action pattern with ARE-HuR interactions and may involve in the post-transcriptional regulation of the HOX11 gene.