The two subunits of human molybdopterin synthase: evidence for a bicistronic messenger RNA with overlapping reading frames

Molybdoenzymes are ubiquitous and require a prosthetic group called the mol ybdenum cofactor for activity. We provide evidence here that the two hetero meric subunits (MOCO1-A and MOCO1-B) of human molybdopterin synthase, which is involved in the conversion of precursor Z to molybdopterin in the molyb denum cofactor biosynthetic pathway, are specified by a single bicistronic mRNA with overlapping reading frames. The transcript is in low abundance an d shows variable tissue distribution. We propose that leaky scanning of the first translational initiation codon for MOCO1-A by 40S ribosomal subunits occurs, allowing recognition of the AUG for the downstream MOCO1-B reading frame. Such a genetic arrangement may result in a constant ratio and close proximity of lowly expressed enzyme subunits which should, a priori, be es pecially advantageous for assembly in complex mammalian cells. The MOCO1 lo cus resides on human chromosome 5.