Pre- and post-transcriptional regulation of the Menkes disease gene

Abstract

Menkes disease is testament to a copper (Cu)-ATPase (ATP7A) playing a dominant role in the absorption and homeostasis of Cu. Significantly, the proximal promoter region of the Menkes disease gene (MNK) has cis-active elements that relate to binding sites for transcription factors which in yeast are known to be activated by a low Cu status. A response to low Cu has not been rationalized into the control of Menkes gene expression, but seems important in light of recent Cu absorption studies in humans. The ATP7A gene gives rises to alternative transcripts, one of which has an insert at the 5′ end with sequence information for a protein with a structural domain similar to a Golgi tethering protein. This has opened speculation that one alternative transcript product may have an important biological function in regulating the entrance of ATP7A laded vesicles into the secretory pathway. This paper presents evidence supporting promoter activation and alternative splicing, pre- and post-transcription events respectively, in the control of Menkes disease gene expression. J. Trace Elem. Exp. Med. 16:181–189, 2003. © 2003 Wiley-Liss, Inc.