The Saccharomyces cerevisiae Hot1p regulated gene YHR087W (HGI1) has a role in translation upon high glucose concentration stress

Abstract

BackgroundWhile growing in natural environments yeasts can be affected by osmotic stress provoked by high glucose concentrations. The response to this adverse condition requires the HOG pathway and involves transcriptional and posttranscriptional mechanisms initiated by the phosphorylation of this protein, its translocation to the nucleus and activation of transcription factors. One of the genes induced to respond to this injury is YHR087W. It encodes for a protein structurally similar to the N-terminal region of human SBDS whose expression is also induced under other forms of stress and whose deletion determines growth defects at high glucose concentrations.ResultsIn this work we show that YHR087W expression is regulated by several transcription factors depending on the particular stress condition, and Hot1p is particularly relevant for the induction at high glucose concentrations. In this situation, Hot1p, together to Sko1p, binds to YHR087W promoter in a Hog1p-dependent manner. Several evidences obtained indicate Yhr087wp’s role in translation. Firstly, and according to TAP purification experiments, it interacts with proteins involved in translation initiation. Besides, its deletion mutant shows growth defects in the presence of translation inhibitors and displays a slightly slower translation recovery after applying high glucose stress than the wild type strain. Analyses of the association of mRNAs to polysome fractions reveals a lower translation in the mutant strain of the mRNAs corresponding to genes GPD1, HSP78 and HSP104.ConclusionsThe data demonstrates that expression of Yhr087wp under high glucose concentration is controlled by Hot1p and Sko1p transcription factors, which bind to its promoter. Yhr087wp has a role in translation, maybe in the control of the synthesis of several stress response proteins, which could explain the lower levels of some of these proteins found in previous proteomic analyses and the growth defects of the deletion strain.

Defining the RNA interactome by total RNA ‐associated protein purification

“…A poorly characterized protein, Rtc3/Hgi1 showed sevenfold increased RNA binding upon sorbic acid treatment. Rtc3 was previously suggested to enhance translation of stress‐response proteins (Gomar‐Alba et al , ), and Rtc3 over‐expression confers resistance to weak acids (Hasunuma et al , ).…”

Molecular basis of the human ribosomopathy Shwachman-Diamond syndrome

“…2B). The fold of the SBDS N-terminal or FYSH (Fungal, Yhr087w, Shwachman) domain (residues S2—S96) is shared with a single-domain yeast protein (Yhr087w) (Shammas et al., 2005) that appears to be involved in translational regulation (Gomar-Alba et al., 2012). The SBDS central domain (residues D97-A170) comprises a three-helical, right-handed twisted bundle, while the C-terminal domain (residues H171-E250) has a ferredoxin-like fold with striking structural similarity to domain V of elongation factor 2 (and EFL1) (Shammas et al., 2005).…”

Defining the RNA Interactome by Total RNA-Associated Protein Purification

“…A poorly characterized protein, Rtc3/Hgi1 showed 7-fold increased RNA-binding upon sorbic acid treatment. Rtc3 was previously suggested to enhance translation of stress-response proteins (Gomar-Alba et al, 2012) and Rtc3 over-expression confers resistance to weak acids (Hasunuma et al, 2016).…”