Biology subjects

Biryukova, I.

Publications and source records attributed to Biryukova, I..

7 recordsLinked to original sources

bioRxiv2024

MirGeneDB 3.0: Improved taxonomic sampling, uniform nomenclature of novel conserved microRNA families, and updated covariance models.

We present a major update of MirGeneDB (3.0), the manually curated animal microRNA gene database. Beyond moving to a new server and the creation of a computational mirror, we have expanded the database with the addition of 33 invertebrate species, including representatives of 5 previously unsampled phyla, and 6 mammal species. MirGeneDB now contains entries for 21, 822 microRNA genes (5, 160 of these from the new species) belonging to 1743 microRNA families. The inclusion of these new species allowed us to refine both the evolutionary node of appearance of a number of microRNA genes/families, as well as MirGeneDBs phylogenetically informed nomenclature system. Updated covariance models of all microRNA families, along with all smallRNA read data are now downloadable. These enhanced annotations will allow researchers to analyze microRNA properties such as secondary structure and features of their biogenesis within a robust phylogenetic context and without the database plagued with numerous false positives and false negatives. In light of these improvements, MirGeneDB 3.0 will assume the responsibility for naming conserved novel metazoan microRNAs. MirGeneDB is part of RNAcentral and Elixir Norway, and is publicly and freely available at master.cloud.mirgenedb.org. Key PointsO_LIMajor update to the manually curated and uniformly named microRNA gene database MirGeneDB C_LIO_LI114 animal species, >1700 microRNA families and [~]20 000 genes searchable, browsable and downloadable C_LIO_LINew features to download all smallRNA read data and updated covariance models for each family C_LI

evolutionary biology↗

bioRxiv2024

Landscape of microRNA and target expression variation and covariation in single mouse embryonic stem cells

MicroRNAs are small RNA molecules that can repress the expression of protein coding genes post-transcriptionally. Previous studies have shown that microRNAs can also have alternative functions including target noise buffering and co-expression, but these observations have been limited to a few microRNAs. Here we systematically study microRNA alternative functions in mouse embryonic stem cells, by genetically deleting Drosha - leading to global loss of microRNAs. We apply complementary single-cell RNA-seq methods to study the variation of the targets and the microRNAs themselves, and transcriptional inhibition to measure target half-lives. We find that microRNAs form four distinct co-expression groups across single cells. In particular the mir-290 and the mir-182 clusters are abundantly, variably and inversely expressed. Intriguingly, some cells have global biases towards specific miRNAs originating from either end of the hairpin precursor, suggesting the presence of unknown regulatory cofactors. We find that miRNAs generally increase variation and covariation of their targets at the RNA level, but we also find miRNAs such as miR-182 that appear to have opposite functions. In particular, miRNAs that are themselves variable in expression, such as miR-291a, are more likely to induce covariations. In summary, we apply genetic perturbation and multi-omics to give the first global picture of microRNA dynamics at the single cell level.

genomics↗

bioRxiv2023

Evolution of microRNAs in Amoebozoa and implications for the origin of multicellularity

MicroRNAs (miRNAs) are important and ubiquitous regulators of gene expression in both plants and animals. They are thought to have evolved convergently in these lineages and hypothesized to have played a role in the evolution of multicellularity. In line with this hypothesis, miRNAs have so far only been described in few unicellular eukaryotes. Here, we investigate the presence and evolution of miRNAs in Amoebozoa, focusing on species belonging to Acanthamoeba, Physarum, and dictyostelid taxonomic groups, representing a range of unicellular and multicellular lifestyles. miRNAs that adhere to both the stringent plant and animal miRNA criteria were identified in all examined amoebae, greatly expanding the total number of protists harbouring miRNAs. We found conserved miRNAs between closely related species, but the majority of species feature only unique miRNAs. Our results show that miRNAs are rapidly lost and gained in Amoebozoa, and that miRNAs were not required for transition from uni- to multicellular life.

evolutionary biology↗

bioRxiv2022

agoTRIBE detects miRNA-target interactions transcriptome-wide in single cells

MicroRNAs are gene regulatory molecules that play important roles in numerous biological processes including human health. The function of a given microRNA is defined by its selection of target transcripts, yet current state-of-the-art experimental methods to identify microRNA targets are laborious and require millions of cells. We have overcome these limitations by fusing the microRNA effector protein Argonaute2 to the RNA editing domain of ADAR2, allowing for the first time the detection of microRNA targets transcriptome-wide in single cells. Our agoTRIBE method reports functional microRNA targets which are additionally supported by evolutionary sequence conservation. As a proof-of-principle, we study microRNA interactions in single cells, and find substantial differential targeting across the cell cycle. Lastly, agoTRIBE additionally provides transcriptome-wide measurements of RNA abundance and will allow the deconvolution of microRNA targeting in complex samples such as tissues at the single-cell level.

genomics↗

bioRxiv2022

Single-cell transcriptomics to define Plasmodium falciparum stage-transition in the mosquito midgut

Malaria inflicts the highest rate of morbidity and mortality among the vector-borne diseases. The dramatic bottleneck of parasite numbers that occurs in the gut of the obligatory vector mosquito provides a promising target for novel control strategies. Using single-cell transcriptomics, we analyzed Plasmodium falciparum development in the mosquito gut, from unfertilized female gametes through the first 20 hours post blood feeding, including the zygote and ookinete stages. This study revealed the transcriptional trajectories of the ApiAP2 family of transcription factors, and of parasite stress genes in response to the harsh environment of the mosquito midgut. Further, employing structure-based functional predictions we found several upregulated genes predicted to encode intrinsically disordered proteins (IDPs), a category of proteins known for their importance in regulation of transcription, translation and protein-protein interactions. IDPs are known for their antigenic properties and may serve as suitable targets for antibody or peptide-based transmission suppression strategies.

microbiology↗

bioRxiv2021

MapToCleave: high-throughput profiling of microRNA biogenesis in living cells

Previous large-scale studies have uncovered many features that determine the processing of microRNA (miRNA) precursors, however, they have been conducted in vitro. Here we introduce MapToCleave, a new method to simultaneously profile processing of thousands of distinct RNA structures in living cells. Our new in cell method captures essentially all the biogenesis features that have been discovered through near two decades of in vitro studies - providing support for both approaches. We find that miRNA precursors with a stable lower basal stem are more efficiently processed and also have higher expression in vivo in tissues from twenty animal species. We systematically compare the importance of known and novel sequence and structural features and test biogenesis of miRNA precursors from ten animal and plant species in human cells. Lastly, we provide evidence that the GHG motif better predicts processing when defined as a structure rather than sequence motif, consistent with recent cryo-EM studies. In summary, we apply a new screening assay in living cells to reveal the importance of lower basal stem stability for miRNA processing and in vivo expression.

molecular biology↗

bioRxiv2019

Nuclear gene proximity and protein interactions shape transcript covariances in mammalian single cells

Single-cell RNA sequencing studies into gene co-expression patterns could yield important new regulatory and functional insights, but have so far been limited by the confounding effects of cell differentiation and the cell cycle. We apply a tailored experimental design that eliminates these confounders, and report >80,000 intrinsically covarying gene pairs in mouse embryonic stem cells. These covariances form a network with biological properties, outlining known and novel gene interactions. We provide the first evidence that miRNAs naturally induce transcriptome-wide covariances, and compare the relative importance of nuclear organization, transcriptional and post-transcriptional regulation in defining covariances. We find that nuclear organization has the greatest impact, and that genes encoding for physically interacting proteins specifically tend to covary, suggesting importance for protein complex stoichiometry. Our results lend support to the concept of post-transcriptional RNA operons, but we further present evidence that nuclear proximity of genes on the same or even distinct chromosomes also provides substantial functional regulation in mammalian single cells.

systems biology↗