The Role of Vts1/Smaug in Adaptive Heritable Gene Expression

Abstract

The ancient RNA Binding Protein (RBP) Vts1 has been identified to self‐assemble along with the Smaug regulator to produce enhancing non‐amyloid prions in mRNA decay. Seen in Drosophila, the sterile‐alpha‐motif (SAM) domain of Vts and the Smaug regulator acts as an embryonic regulator for maternal transcript degradation through cytoplasmic deadenylase in progeny development. Specifically, of Saccharomyces cerevisiae, the Vts/Smaug regulator forms condensates that self‐template to create prions functioning towards epigenetic heritable inheritance. The RBP Vts1 SAM domain recognizes in RNA hairpins Smaug recognition elements, SREs, initiating the process of degradation and self‐assembly. The structure of RBPs are composed of an ordered RNA binding domain, and an unventured intrinsically disordered region (IDR). At the quaternary level structure, the Vts1 protein matches as a hexamer of 489 kDa dominant peak with an oligomer of more than eight monomers, and the IDR is around 490 kDa as well while the RBD‐Vts1 is around 75 kDa. The condensed version of Vts1 fuse into structures of 10 micrometers due to the IDR driving self‐association to create oligomers. The RNA binding SAM domain and IDR have induced transcription degradation and post‐transcriptional regulation in a new mechanism, prompting adaptive gene expression for developmental decisions in organisms over evolutionary time periods. Though many RBP prion condensates are not heritable and inactivate protein function, the SMAUG+ prions of the condensed Vts1/Smaug protein in S. Cerevisiae instead respond to environmental stress and produce new emerging phenotypes that are actually heritable over a large biological time‐scale. Furthermore, SMAUG+ conversion is reversible and an enhancer of RBP Vts1 function, producing adaptive gene expression systems in fluctuating environments. In various yeast models, the SMAUG+ allows yeast to decide nutrient replenishment after starvation which creates a new adaptive advantage for organisms. The new cellular decision making regulated by the prion is in two forms of rapid mitosis or meiosis creating a non‐stress state; SMAUG+ has created an adaptive memory that can influence developmental and cellular decisions in addition to plant growth in limited nutrients. Such advancements in heritable prion inheritance can uncover the function of intrinsically disordered sequences. The Walton SMART team has designed a 3D model with MSOE Center for Biomolecular Modeling to investigate the SAM domain of Vts1 further and examine the role of SMAUG+ prions in adaptive heritable gene expression.