Evolutionary roles of upstream open reading frames in mediating gene regulation in fungi.

Upstream open reading frames (uORFs) are frequently present in the 5'-leader regions of fungal mRNAs. They can affect translation by controlling the ability of ribosomes that scan from the mRNA 5' end to reach the downstream genic reading frame. The translation of uORFs can also affect mRNA stability. For several genes, including Saccharomyces cerevisiae GCN4, S. cerevisiae CPA1, and Neurospora crassa arg-2, regulation by uORFs controls expression in response to specific physiological signals. The roles of many uORFs that are identified by genome-level approaches, as have been initiated for Saccharomyces, Aspergillus, and Cryptococcus species, remain to be determined. Some uORFs may have regulatory roles, while others may exist to insulate the genic reading frame from the negative impacts of upstream translation start sites in the mRNA 5' leader.