RrmA regulates the stability of specific transcripts in response to both nitrogen source and oxidative stress.

Differential regulation of transcript stability is an effective means by which an organism can modulate gene expression. A well-characterized example is glutamine signalled degradation of specific transcripts in Aspergillus nidulans. In the case of areA, which encodes a wide-domain transcription factor mediating nitrogen metabolite repression, the signal is mediated through a highly conserved region of the 3' UTR. Utilizing this RNA sequence we isolated RrmA, an RNA recognition motif protein. Disruption of the respective gene led to loss of both glutamine signalled transcript degradation as well as nitrate signalled stabilization of niaD mRNA. However, nitrogen starvation was shown to act independently of RrmA in stabilizing certain transcripts. RrmA was also implicated in the regulation of arginine catabolism gene expression and the oxidative stress responses at the level of mRNA stability. ΔrrmA mutants are hypersensitive to oxidative stress. This phenotype correlates with destabilization of eifE and dhsA mRNA. eifE encodes eIF5A, a translation factor within which a conserved lysine is post-translationally modified to hypusine, a process requiring DhsA. Intriguingly, for specific transcripts RrmA mediates both stabilization and destabilization and the specificity of the signals transduced is transcript dependent, suggesting it acts in consort with other factors which differ between transcripts.

Arginine catabolism in Aspergillus nidulans is regulated by the rrmA gene coding for the RNA-binding protein.

Expression of Aspergillus nidulans arginine catabolism genes, agaA and otaA, is regulated at the level of transcription by a specific induction and two global carbon and nitrogen repression systems. Post-transcriptional and/or post-translational mechanisms have also been proposed to operate additionally. Gene tagging with transposon impala allowed us to select the rrmA gene. RRMA protein contains three conserved RRM domains, typical for RNA-binding proteins. The gene has a complex structure with several potential transcription start sites, an exceptionally long intron in 5'UTR and few uORFs in the intron. RRMA is highly conserved among fungi. Its homologues, Csx1p of Schizosaccharomyces pombe and Ngr1p of Saccharomyces cerevisiae, participate in the post-transcriptional regulation of specific genes by modifying transcript stability. Levels of otaA and agaA transcripts in the rrmA::impala loss of function mutant grown under inducing conditions are significantly higher than in the wild type strain. We propose that RRMA participates in a mechanism promoting agaA and otaA mRNA degradation. The rrmA::impala mutation has pleiotropic character and results in a slow growth phenotype indicating that rrmA functions are not limited to the regulation of arginine catabolism.