Biology subjects

Rubanova, N.

Publications and source records attributed to Rubanova, N..

4 recordsLinked to original sources

bioRxiv2025

An endogenous retroviral element co-opts an upstream regulatory sequence to achieve somatic expression and mobility

Retrotransposons, multi-copy sequences that propagate via copy-and-paste mechanisms involving an RNA intermediate, occupy large portions of all eukaryotic genomes. A great majority of their manifold copies remain silenced in somatic cells, nevertheless, some are transcribed, often in a tissue specific manner, and a small fraction retains its ability to mobilize. Retrotransposon expression or mobility are increasingly recognized to contribute to normal development and tissue homeostasis, as well as to aging and disease. While it is well characterized that retrotransposon sequences may provide cis regulatory elements for neighboring genes, how their own expression and mobility are achieved in different somatic contexts is not well understood. Here, using long-read DNA sequencing, we characterize somatic retrotransposition in the Drosophila intestine. We show that retroelement mobility does not change significantly upon aging and is limited to very few active sub-families of retrotransposons. Importantly, we identify a polymorphic donor locus of an endogenous LTR retroviral element rover, active in the intestinal tissue. We reveal that gut activity of the rover donor copy depends on its genomic environment. Without affecting local gene expression, the copy co-opts its upstream enhancer sequence, rich in transcription factor binding sites, for somatic expression. Further we show that escargot, a snail-type transcription factor critical for gut progenitor cell function, can drive transcriptional activity of the active rover copy. These data provide new insights into how locus-specific features allow active retrotransposons to produce functional transcripts and mobilize in a somatic lineage.

genomics↗

bioRxiv2022

Molecular Underpinnings and Environmental Drivers of Spontaneous Loss of Heterozygosity in Drosophila Intestinal Stem Cells

The genome stability of adult stem cells is of particular importance as these cells maintain long-term self-renewal capacity and can contribute extensively to adult tissues. During development and aging, genome mutation leading to loss of heterozygosity (LOH) can uncover recessive phenotypes and be propagated within tissue compartments. This phenomenon occurs in normal human tissues, and is prevalent in pathological genetic conditions and cancers. While previous studies in yeast have defined distinct DNA repair mechanisms that can promote LOH, the predominant pathways underlying LOH in complex somatic tissues of multicellular organisms arenot well understood. In addition, how environmental triggers such as pathogenic bacterial infection may impact LOH is unclear. Here, we investigate the mechanisms giving rise to LOH in adult intestinal stem cells in Drosophila. Our data indicate that infection with the enteric pathogenic bacteria, Erwinia carotovora carotovora 15 but not Pseudomonas entomophila increases LOH frequency. Using whole-genome sequencing of somatic LOH events, we demonstrate that they arise primarily via mitotic recombination. Molecular features of recombination sites and genetic evidence argue against formation via break-induced replication and instead support cross-over events arising from double Holliday junction-based repair. This study provides a mechanistic understanding of mitotic recombination in stem cells in vivo, an important mediator of LOH.

developmental biology↗

bioRxiv2018

MasterPATH: network analysis of functional genomics screening data

Functional genomics employs several experimental techniques to investigate gene functions. These techniques such as loss-of-function screening and transcriptome profiling performed in a high-throughput manner give as result a list of genes involved in the biological process of interest. There exist several computational methods for analysis and interpretation of the list. The most widespread methods aim at investigation of biological processes significantly represented in the list or at extracting significantly represented subnetworks. Here we present a new exploratory network analysis method that employs the shortest path approach and centrality measure to uncover members of active molecular pathways leading to the studied phenotype based on the results of functional genomics screening data. We present the method and we demonstrate what data can be retrieved by its application to the terminal muscle differentiation miRNA loss-of-function screening and transcriptomic profiling data and to the druggable loss-of-function RNAi screening data of the DNA repair process.

systems biology↗

bioRxiv2018

Centrality and the shortest path approach on the human interactome

A network is one of the most convenient way to represent interactions between biological entities in systems biology. A network of molecular interactions is a graph in which the vertices are biological component and the edges correspond to the interactions between them. Many notions and approaches for network analysis came to systems biology from the theory of graphs - a field of mathematics that study graphs. We focused on the study of the shortest path approach in this work. We investigated whether this approach yields valid molecular paths. To perform this, the shortest paths in the human interactome (derived from HPRD and HIPPIE databases) were found between all relevant combinations of proteins taken from eight well-studied highly conserved signaling pathways from the KEGG database (NF-kappa B, MAPK, Jak-STAT, mTOR, ErbB, Wnt, TGF-beta and the signaling part of the apoptotic process). Canonical paths were systematically compared with the shortest counterparts and centrality of vertices and paths in subnetworks induced by the shortest paths were analyzed. We found that the sets of the shortest paths contain the canonical counterparts only for very short canonical paths (length 2-3 interactions). We also found that high centrality vertices tend to belong to canonical counterparts, to less extent this can also be said about high centrality paths.

systems biology↗