Introns in yeast regulate translation to generate protein and cellular function

Abstract

While RNA splicing has been recognized as an important mode of eukaryotic gene regulation, the role that introns themselves play in gene expression and proteome diversity has been less clear. Here, we describe how the intron of GCR1, a transcription factor that regulates glycolytic gene expression, contains intronic elements that control translation initiated from an in‐frame, intronic‐AUG. Moreover, the intronic elements regulate translation under stress conditions. To understand how the translation start site within the intron is recognized, we analyzed the structures and functions of sequences around the start site. These studies reveal an internal ribosome entry site (IRES) that regulates translation initiation from within the intron. In addition to this sequence, we find that a ribosomal protein, Rps25, regulates utilization of the intronic AUG. These data suggest that splicing regulation and intron retention set up a novel mode of translational control. When we analyzed all intron‐containing genes in yeast, we discovered that this architecture—an intronic AUG that is in frame with the annotated stop codon—is found in other intron‐containing genes. Moreover, the proteins generated appear to be functional, particularly under stress conditions. Together these studies illustrate a role for introns in translational control and tuning the proteome in response to environmental conditions.