Originally published as Genetics Published Articles Ahead of Print on February 16, 2009.

Genetics, Vol. 181, 1261-1272, April 2009, Copyright © 2009
doi:10.1534/genetics.108.099515

Phenotypes of Mutations in the 5'-UTR of a Limiting Transcription Factor in Aspergillus nidulans Can Be Accounted For by Translational Inhibition and Leaky Scanning

Nathalie Oestreicher*,1 and Claudio Scazzocchio*,{dagger}

* Université Paris XI, CNRS UMR8621, Institut de Génétique et Microbiologie, 91405 Orsay Cedex, France and {dagger} Department of Microbiology, Imperial College, London SW7 2AZ, United Kingdom

1 Corresponding author: Institut de Génétique et Microbiologie, Bâtiment 360, Université Paris XI, 91405 Orsay Cedex, France.
E-mail: nathalie.oestreicher{at}igmors.u-psud.fr

The uaY gene encodes the transcriptional activator of purine catabolism genes in Aspergillus nidulans. uaY12 results in strongly defective growth on purines as nitrogen sources and in strongly diminished transcription of UaY-regulated genes. This mutation introduces an ATG codon 64 bp upstream of the uaY ATG, generating a 68-codon open reading frame (uORFA), overlapping with the uaY ORF. uaY12 revertants fall into three categories:

  1. The majority eliminate the aberrant ATG. The growth and transcriptional phenotypes of these revertants are identical to those of the wild type.
  2. Two revertants create a stop codon in frame with the uaY12 aberrant ATG, shortening the length of the uORFA, thus uORFA no longer overlaps the uaY ORF. The latter are partial suppressors of the uaY12 mutation, while chain termination suppressors, in turn, suppress this novel phenotype.
  3. Two partial suppressors are unlinked to uaY. These two mutations result in a pleiotropic phenotype usually associated with ribosomal proteins.

We hypothesize that uORFA strongly diminishes translation of the uaY ORF and that revertants negate this effect by a number of different mechanisms. The first-AUG rule and the phenomena of translational inhibition and leaky scanning provide a coherent explanation of the results presented in this article.