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RNA. 2000 Jul; 6(7): 928–936.
PMCID: PMC1369970

Diverse splicing mechanisms fuse the evolutionarily conserved bicistronic MOCS1A and MOCS1B open reading frames.

Abstract

Molybdenum is an essential cofactor in many enzymes, but must first be complexed by molybdopterin, whose synthesis requires four enzymatic activities. The first two enzymes of this pathway are encoded by the MOCS1 locus in humans. We describe here a remarkably well-conserved novel mRNA splicing phenomenon that produces both an apparently bicistronic MOCS1AM-OCS1B transcript, as well as a distinct class of monocistronic transcript. The latter are created by a variety of splicing mechanisms (alternative splice donors, alternative splice acceptors, and exon-skipping) to bypass the normal termination nonsense codon of MOCS1A resulting in fusion of the MOCS1A and MOCS1B open reading frames. Therefore, these "no-nonsense" transcripts encode a single bifunctional protein embodying both MOCS1A and MOCS1B activities. This coexpression profile was observed in vertebrates (human, mouse, cow, rabbit, opossum, and chicken) and invertebrates (fruit fly and nematode) spanning at least 700 million years of evolution. Our phylogenetic data also provide evidence that the bicistronic form of MOCS1 mRNA is likely to only produce MOCS1A protein and, combined with Northern analyses, suggests that MOCS1B is translated only as a fusion with MOCS1A. Taken together, the data presented here demonstrate a very highly conserved and physiologically relevant dynamic splicing scheme that profoundly influences the protein-coding potential of the MOCS1 locus.

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Selected References

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  • Blumenthal T. Trans-splicing and polycistronic transcription in Caenorhabditis elegans. Trends Genet. 1995 Apr;11(4):132–136. [PubMed]
  • Blumenthal T. Gene clusters and polycistronic transcription in eukaryotes. Bioessays. 1998 Jun;20(6):480–487. [PubMed]
  • Enright AJ, Iliopoulos I, Kyrpides NC, Ouzounis CA. Protein interaction maps for complete genomes based on gene fusion events. Nature. 1999 Nov 4;402(6757):86–90. [PubMed]
  • Gray TA, Saitoh S, Nicholls RD. An imprinted, mammalian bicistronic transcript encodes two independent proteins. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5616–5621. [PMC free article] [PubMed]
  • Grundner-Culemann E, Martin GW, 3rd, Harney JW, Berry MJ. Two distinct SECIS structures capable of directing selenocysteine incorporation in eukaryotes. RNA. 1999 May;5(5):625–635. [PMC free article] [PubMed]
  • Haas AL, Siepmann TJ. Pathways of ubiquitin conjugation. FASEB J. 1997 Dec;11(14):1257–1268. [PubMed]
  • Hayward BE, Moran V, Strain L, Bonthron DT. Bidirectional imprinting of a single gene: GNAS1 encodes maternally, paternally, and biallelically derived proteins. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15475–15480. [PMC free article] [PubMed]
  • Hochstrasser M. Ubiquitin-dependent protein degradation. Annu Rev Genet. 1996;30:405–439. [PubMed]
  • Hoff T, Schnorr KM, Meyer C, Caboche M. Isolation of two Arabidopsis cDNAs involved in early steps of molybdenum cofactor biosynthesis by functional complementation of Escherichia coli mutants. J Biol Chem. 1995 Mar 17;270(11):6100–6107. [PubMed]
  • Ischia R, Lovisetti-Scamihorn P, Hogue-Angeletti R, Wolkersdorfer M, Winkler H, Fischer-Colbrie R. Molecular cloning and characterization of NESP55, a novel chromogranin-like precursor of a peptide with 5-HT1B receptor antagonist activity. J Biol Chem. 1997 Apr 25;272(17):11657–11662. [PubMed]
  • Kozak M. Initiation of translation in prokaryotes and eukaryotes. Gene. 1999 Jul 8;234(2):187–208. [PubMed]
  • Low SC, Berry MJ. Knowing when not to stop: selenocysteine incorporation in eukaryotes. Trends Biochem Sci. 1996 Jun;21(6):203–208. [PubMed]
  • Marcotte EM, Pellegrini M, Ng HL, Rice DW, Yeates TO, Eisenberg D. Detecting protein function and protein-protein interactions from genome sequences. Science. 1999 Jul 30;285(5428):751–753. [PubMed]
  • Marcotte EM, Pellegrini M, Thompson MJ, Yeates TO, Eisenberg D. A combined algorithm for genome-wide prediction of protein function. Nature. 1999 Nov 4;402(6757):83–86. [PubMed]
  • Peters J, Wroe SF, Wells CA, Miller HJ, Bodle D, Beechey CV, Williamson CM, Kelsey G. A cluster of oppositely imprinted transcripts at the Gnas locus in the distal imprinting region of mouse chromosome 2. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3830–3835. [PMC free article] [PubMed]
  • Reiss J, Christensen E, Dorche C. Molybdenum cofactor deficiency: first prenatal genetic analysis. Prenat Diagn. 1999 Apr;19(4):386–388. [PubMed]
  • Reiss J, Christensen E, Kurlemann G, Zabot MT, Dorche C. Genomic structure and mutational spectrum of the bicistronic MOCS1 gene defective in molybdenum cofactor deficiency type A. Hum Genet. 1998 Dec;103(6):639–644. [PubMed]
  • Reiss J, Cohen N, Dorche C, Mandel H, Mendel RR, Stallmeyer B, Zabot MT, Dierks T. Mutations in a polycistronic nuclear gene associated with molybdenum cofactor deficiency. Nat Genet. 1998 Sep;20(1):51–53. [PubMed]
  • Reiss J, Dorche C, Stallmeyer B, Mendel RR, Cohen N, Zabot MT. Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B. Am J Hum Genet. 1999 Mar;64(3):706–711. [PMC free article] [PubMed]
  • Sloan J, Kinghorn JR, Unkles SE. The two subunits of human molybdopterin synthase: evidence for a bicistronic messenger RNA with overlapping reading frames. Nucleic Acids Res. 1999 Feb 1;27(3):854–858. [PMC free article] [PubMed]
  • Stallmeyer B, Drugeon G, Reiss J, Haenni AL, Mendel RR. Human molybdopterin synthase gene: identification of a bicistronic transcript with overlapping reading frames. Am J Hum Genet. 1999 Mar;64(3):698–705. [PMC free article] [PubMed]
  • Stallmeyer B, Schwarz G, Schulze J, Nerlich A, Reiss J, Kirsch J, Mendel RR. The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1333–1338. [PMC free article] [PubMed]
  • Unkles SE, Smith J, Kanan GJ, Millar LJ, Heck IS, Boxer DH, Kinghorn JR. The Aspergillus nidulans cnxABC locus is a single gene encoding two catalytic domains required for synthesis of precursor Z, an intermediate in molybdenum cofactor biosynthesis. J Biol Chem. 1997 Nov 7;272(45):28381–28390. [PubMed]

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