TY  - JOUR
A1  - Hahnewald, Rita
A1  - Leimkühler, Silke
A1  - Vilaseca, Antonia
A1  - Acquaviva-Bourdain, Cecile
A1  - Lenz, Ulrike
A1  - Reiss, Jochen
T1  - A novel MOCS2 mutation reveals coordinated expression of the small and large subunit of molybdopterin synthase
JF  - Molecular genetics and metabolism
N2  - 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.
KW  - molybdenum cofactor deficiency
KW  - MOCS2
KW  - overlapping reading frames
Y1  - 2006
U6  - https://doi.org/10.1016/j.ymgme.2006.04.008
SN  - 1096-7192
VL  - 89
IS  - 3
SP  - 210
EP  - 213
PB  - Elsevier
CY  - San Diego
ER  - 
TY  - JOUR
A1  - Leimkühler, Silke
A1  - Charcosset, M.
A1  - Latour, P.
A1  - Dorche, C.
A1  - Kleppe, S.
A1  - Scaglia, F.
A1  - Szymczak, I.
A1  - Schupp, P.
A1  - Hahnewald, Rita
A1  - Reiss, J.
T1  - Ten novel mutations in the molybdenum cofactor genes MOCS1 and MOCS2 and in vitro characterization of a MOCS2 mutation that abolishes the binding ability of molybdopterin synthase
N2  - Molybdenum cofactor deficiency (MIM#252150) is a severe autosomal- recessive disorder with a devastating outcome. The cofactor is the product of a complex biosynthetic pathway involving four different genes (MOCS1, MOCS2, MOCS3 and GEPH). This disorder is caused almost exclusively by mutations in the MOCS1 or MOCS2 genes. Mutations affecting this biosynthetic pathway result in a lethal phenotype manifested by progressive neurological damage via the inactivation of the molybdenum cofactor-dependent enzyme, sulphite oxidase. Here we describe a total of ten novel disease-causing mutations in the MOCS1 and MOCS2 genes. Nine out of these ten mutations were classified as pathogenic in nature, since they create a stop codon, affect constitutive splice site positions, or change strictly conserved motifs. The tenth mutation abolishes the stop codon of the MOCS2B gene, thus elongating the corresponding protein. The mutation was expressed in vitro and was found to abolish the binding affinities of the large subunit of molybdopterin synthase (MOCS2B) for both precursor Z and the small subunit of molybdopterin synthase (MOCS2A)
Y1  - 2005
SN  - 0340-6717
ER  -