Biology subjects

Rezvykh, A. P.

Publications and source records attributed to Rezvykh, A. P..

3 recordsLinked to original sources

bioRxiv2024

The biological consequences of knockout of genes involved in the synthesis and metabolism of H2S in Drosophila melanogaster

Here, we describe the effect of knockout (KO) of two key genes (cbs, cse) responsible for H2S synthesis in the transsulfuration pathway as well as the inactivation of sulfurtransferase gene (dtst1) encoding single domain rhodanese on Drosophila melanogaster genome expression and several life-history traits. The analysis of H2S production in the KO flies showed its minimal level in the strain with double KO (CBS-/-; CSE-/-) while flies with triple KO (CBS-/-; CSE-/-; dTST1-/-) exhibited higher H2S level and improvements in lifespan. The transcriptomic analysis of fly bodies from the double KO strain with maximum disturbances of fitness components revealed a profound increase in the expression of genes involved in the functioning of the excretory system. Besides, double and triple KO flies exhibited drastic changes in Malpighian tubules appearance. Inactivation of genes related to H2S metabolism resulted in altered expression of numerous loci involved in mitochondrial function. While KO of the dtst1 gene did not affect the genome expression, the triple KO flies exhibited more changes in the whole-body transcriptome than double KO flies. Reduced fecundity in double knockouts correlates with pronounced changes in ovarian transcriptome data. Surprisingly, the knockout of the dtst1 gene affected the flies memory.

molecular biology↗

bioRxiv2019

Insulator proteins contribute to expression of gene loci repositioned into heterochromatin in the course of Drosophila evolution

Pericentric heterochromatin in Drosophila is generally composed of repetitive DNA forming a transcriptionally repressive environment. Nevertheless, dozens of genes were embedded into pericentric genome regions during evolution of Drosophilidae lineage and retained functional activity. However, factors that contribute to \"immunity\" of these gene loci to transcriptional silencing remain unknown. Here, we investigated molecular evolution of the essential Myb and Ranbp16 genes. These protein-coding genes reside in euchromatic loci of chromosome X in D. melanogaster and related species, while in other studied Drosophila species, including evolutionary distant ones, they are located in genomic regions highly enriched with the remnants of transposable elements (TEs), suggesting their heterochromatic nature and location. The promoter region of Myb exhibits a conserved structure throughout the Drosophila phylogeny and carries motifs for binding of chromatin remodeling factors, including insulator BEAF-32, regardless of eu- or heterochromatic surroundings. Importantly, BEAF-32 occupies not only the promoter region of Myb but is also found in the vicinity of transcriptional start sites (TSS) of Ranbp16 gene as well as in a wide range of genes located in the contrasting chromatin types in D. melanogaster and D. virilis, denoting the boundary of the nucleosome-free region available for RNA polymerase II recruitment and the surrounding heterochromatin. We also find that along with BEAF-32, insulators dCTCF and GAF are enriched at the TSS of heterochromatic genes in D. melanogaster. Thus, we propose that insulator proteins contribute to gene expression in the heterochromatic environment and, hence, facilitate the evolutionary repositioning of gene loci into heterochromatin.\n\nAuthor summaryHeterochromatin in Drosophila is generally associated with transcriptional silencing. Nevertheless, hundreds of essential genes have been identified in the pericentric heterochromatin of Drosophila melanogaster. Interestingly, genes embedded in pericentric heterochromatin of D. melanogaster may occupy different genomic loci, euchromatic or heterochromatic, due to repositioning in the course of evolution of Drosophila species. By surveying factors that contribute to the normal functioning of the relocated genes in distant Drosophila species, i.e. D. melanogaster and D. virilis, we identify certain insulator proteins (e.g.BEAF-32) that facilitate the expression of heterochromatic genes in spite of the repressive environment.

evolutionary biology↗

bioRxiv2019

Low level of expression of C-terminally truncated human FUS causes extensive changes in spinal cord transcriptome of asymptomatic transgenic mice

Mutations in a gene encoding RNA-binding protein FUS was linked to familial forms of amyotrophic lateral sclerosis (ALS). C-terminal truncations of FUS are associated with aggressive forms of ALS. However, motor neurons are able to tolerate permanent production of pathogenic truncated form of FUS protein until its accumulation in the cytoplasm of neurones does not reach a critical threshold.\n\nIn order to identify how the nervous system responds to pathogenic variants of FUS we produced and characterised a mouse line, L-FUS[1-359], with a low level of neuronal expression of a highly aggregation prone and pathogenic form of C-terminally truncated FUS. In contrast to mice with substantially higher level of expression of the same FUS variant that develop severe early onset motor neuron pathology, L-FUS[1-359] mice do not develop any sign of pathology even at old age. Nevertheless, we detected substantial changes in the spinal cord transcriptome of these mice comparing to the wild type littermates. We suggest that at least some of these changes reflect activation of cellular mechanisms compensating to potentially damaging effect of pathogenic FUS production. Further studies of these mechanism might reveal effective target for therapy of FUS-ALS and possibly, other forms of ALS.

neuroscience↗