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Nonsense-Mediated mRNA Decay Mutation in Aspergillus nidulans

Igor Y. Morozov,¹ Susana Negrete-Urtasun,² Joan Tilburn,² Christine A. Jansen,^2, Mark X. Caddick,¹ and Herbert N. Arst Jr.^2*

School of Biological Sciences, Bioscience Building, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdom,¹ Department of Molecular Microbiology and Infection, Flowers Building, Imperial College London, Armstrong Road, London SW7 2AZ, United Kingdom²

Received 12 July 2006/ Accepted 29 August 2006

An Aspergillus nidulans mutation, designated nmdA1, has been selected as a partial suppressor of a frameshift mutation and shown to truncate the homologue of the Saccharomyces cerevisiae nonsense-mediated mRNA decay (NMD) surveillance component Nmd2p/Upf2p. nmdA1 elevates steady-state levels of premature termination codon-containing transcripts, as demonstrated using mutations in genes encoding xanthine dehydrogenase (hxA), urate oxidase (uaZ), the transcription factor mediating regulation of gene expression by ambient pH (pacC), and a protease involved in pH signal transduction (palB). nmdA1 can also stabilize pre-mRNA (unspliced) and wild-type transcripts of certain genes. Certain premature termination codon-containing transcripts which escape NMD are relatively stable, a feature more in common with certain nonsense codon-containing mammalian transcripts than with those in S. cerevisiae. As in S. cerevisiae, 5' nonsense codons are more effective at triggering NMD than 3' nonsense codons. Unlike the mammalian situation but in common with S. cerevisiae and other lower eukaryotes, A. nidulans is apparently impervious to the position of premature termination codons with respect to the 3' exon-exon junction.

Published ahead of print on 8 September 2006.

Present address: Department of Immunology, UMC Utrecht, Utrecht, The Netherlands.

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