title: A novel MOCS2 mutation reveals coordinated expression of the small and large subunit of molybdopterin synthase.
abstract: The small and large subunits of molybdopterin (MPT) synthase (MOCS2A and MOCS2B), are both encoded by the MOCS2 gene in overlapping and shifted open reading frames (ORFs), which is a highly unusual structure for eukaryotes. Theoretical analysis of genomic sequences suggested that the expression of these overlapping ORFs is facilitated by the use of alternate first exons leading to alternative transcripts. Here, we confirm the existence of these overlapping transcripts experimentally. Further, we identified a deletion in a molybdenum cofactor deficient patient, which removes the start codon for the small subunit (MOCS2A). We observed undisturbed production of both transcripts, while Western blot analysis demonstrated that MOCS2B, the large subunit, is unstable in the absence of MOCS2A. This reveals new insights into the expression of this evolutionary ancient anabolic system.
authors.affiliation: Institut für Humangenetik der Universität Göttingen, Heinrich-Düker-Weg 12, 37073 Göttingen, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Hahnewald
authors.forename: Silke
authors.initials: S
authors.lastname: Leimkühler
authors.forename: Antonia
authors.initials: A
authors.lastname: Vilaseca
authors.forename: Cecile
authors.initials: C
authors.lastname: Acquaviva-Bourdain
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lenz
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiss
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D017809:Fatal Outcome; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008110:Liver Extracts; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism*; D012326:RNA Splicing / Q000235:genetics; D013466:Sulfurtransferases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D008110:Liver Extracts; D021122:Protein Subunits; D013466:Sulfurtransferases; C085585:molybdopterin synthase