Abstract

Across eukaryotes, homopolymeric repeats of amino acids are enriched in regulatory proteins such as transcription factors and chromatin remodelers. These domains play important roles in signaling, binding, prion formation, and functional phase separation. Azf1p is a prion-forming yeast transcription factor that contains two homorepeat domains, a polyglutamine and a polyasparagine domain. In this work, we report a new phenotype for Azf1p and identify a large set of genes that are regulated by Azf1p during growth in glucose. We show that the polyasparagine (polyN) domain plays a subtle role in transcription but is dispensable for Azf1p localization and prion formation. Genes upregulated upon deletion of the polyN domain are enriched in functions related to carbon metabolism and storage. This domain may therefore be a useful target for engineering yeast strains for fermentation applications and small molecule production. We also report that both the polyasparagine and polyglutamine domains vary in length across strains of S. cerevisiae and propose a model for how this variation may impact protein function.

Highlights

  • Repeat domains are prevalent in the eukaryotic proteome and are found in 13% of proteins in yeast, 17% in humans, and 21% in Drosophila

  • Azf1p is a prion-forming yeast transcription factors (TFs) that has been shown to activate genes involved in carbon metabolism and energy production during growth in glucose [10,31]

  • Slattery and colleagues investigated the impact of the null mutant on growth on glucose by spotting assay, which did not reveal any differences between azf1Δ and the WT

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Summary

Introduction

Repeat domains are prevalent in the eukaryotic proteome and are found in 13% of proteins in yeast, 17% in humans, and 21% in Drosophila. Repeats are commonly found within intrinsically disordered regions (IDRs), which are protein domains that do not have a single native fold corresponding to a lowest energy state. Instead, these domains dynamically sample a number of conformations with similar energies [1]. Repeats are enriched in cell-surface and regulatory proteins, such as transcription factors (TFs) and chromatin remodelers [2]. Repeats enriched in a single amino acid are deemed homorepeats. Polyglutamine (polyQ) is the most common type of homorepeat in eukaryotic proteins, followed by polyasparagine (polyN). While polyQ domains are found across eukaryotes, polyN domains are rare in vertebrates and found almost exclusively in more primitive invertebrates

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