Genome-wide transcriptional effects of deletions of sulphur metabolism genes in Drosophila melanogaster

Abstract

In recent years, the gasotransmitter hydrogen sulphide (H 2 S), produced by the transsulphuration pathway, has been recognized as a biological mediator playing an important role under normal conditions and in various pathologies in both eukaryotes and prokaryotes. The transsulphuration pathway (TSP) includes the conversion of homocysteine to cysteine following the breakdown of methionine. In Drosophila melanogaster and other eukaryotes, H 2 S is produced by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulphurtransferase (MST). In the experiments performed in this study, we were able to explore the CRISPR/Cas9 technique to obtain single and double deletions in homozygotes of these three major genes responsible for H 2 S production in Drosophila melanogaster . In most cases, the deletion of one studied gene does not result in the compensatory induction of two other genes responsible for H 2 S production. Transcriptomic studies demonstrated that the deletions of the above CBS and CSE genes alter genome expression to different degrees, with a more pronounced effect being exerted by deletion of the CBS gene. Furthermore, the double deletion of both CBS and CSE resulted in a cumulative effect on transcription in the resulting strains. Overall, we found that the obtained deletions affect numerous genes involved in various biological pathways. Specifically, genes involved in the oxidative reduction process, stress-response genes, housekeeping genes, and genes participating in olfactory and reproduction are among the most strongly affected. Furthermore, characteristic differences in the response to the deletions of the studied genes are apparently organ-specific and have clear-cut sex-specific characteristics. Single and double deletions of the three genes responsible for the production of H 2 S helped to elucidate new aspects of the biological significance of this vital physiological mediator.

Hydrogen Sulfide: An Emerging Precision Strategy for Gas Therapy

“…H 2 S can inhibit mitochondrial function and depress cellular oxygen receptors to reduce the metabolic demand for oxygen. [201][202][203][204][205][206] Blackstone et al demonstrated that 80 ppm of H 2 S suppress metabolism in mice, causing them to enter a hibernation state. [70] However, Drabek et al reported that intravenous H 2 S failed to improve the survival rate of pigs with hemorrhagic shock.…”

Can Blood-Circulating Factors Unveil and Delay Your Biological Aging?

“…Recently, it has been shown that H 2 S is involved in the regulation of the chaperone function. Enzymes controlling the H 2 S production CSE/CTH/CGL (cystathionine-γ lyase), CBS (cystathionine-β-synthase), and MST (3-mercaptopyruvate sulfurtransferase) are implicated in stress resistance, aging, and stress-dependent regulation of HSP22, HSP70, and HSF1 [ 87 , 88 ]. Chaperones play an important role in adaptive stress and can directly regulate the expression of the Foxo3 gene associated with lifespan (Forkhead box O3) [ 89 ].…”

Genes Responsible for H2S Production and Metabolism Are Involved in Learning and Memory in Drosophila melanogaster

“…However, to the best of our knowledge, there are only scattered data implicating the synthesis of endogenous H 2 S in the memory process and mating behavior under normal conditions in higher organisms [ 21 , 22 ]. Drosophila melanogaster strains obtained in our laboratory [ 23 ] containing single and double deletions of the three major genes implicated in H 2 S production represent a convenient model to study the role of H 2 S production in learning and memory processes in higher organisms.…”

“…In the experiments described herein, we made use of several D. melanogaster strains obtained using the CRISPR/Cas9 technique. These strains with deletions of the three genes ( CBS, CSE, and MST ) were used and described in detail in our previous studies [ 23 , 28 ]. Transcriptomic studies demonstrated that the deletions of both CBS and CSE ( CBS-/- ; CSE-/- ) have a cumulative effect and drastically alter genome expression, with a more pronounced impact exerted by the deletion of the CBS gene.…”

“…Transcriptomic studies demonstrated that the deletions of both CBS and CSE ( CBS-/- ; CSE-/- ) have a cumulative effect and drastically alter genome expression, with a more pronounced impact exerted by the deletion of the CBS gene. The previous analysis demonstrated that the obtained deletions of CBS and CSE affected numerous genes involved in various biological pathways including oxidation-reduction process, glutathione metabolic process, stress-response genes, housekeeping genes, and genes participating in olfactory and reproduction, while the deletion of MST affected a comparatively small number of genes [ 23 ]. Based on the above-mentioned facts and considerations, we decided to monitor the learning and memory parameters of these strains ( CBS-/- and CSE-/- ), as well as strains with deletions of both CBS and CSE genes ( CBS-/-; CSE-/- ) using the mating rejection courtship paradigm.…”