Biology subjects

Smirnova, A.

Publications and source records attributed to Smirnova, A..

6 recordsLinked to original sources

bioRxiv2026

Universally conserved isoasparylation sustains ribosome biogenesis and function

All living beings use ribosomes to synthesize proteins from -amino acids. Inherited from our common ancestor, a few universally conserved ribosome biogenesis steps, introducing essential ribosomal RNA modifications, have survived to our days. However, it was unknown whether similar primordial core mechanisms could also target ribosomal proteins. Here we show that the assembly and the function of ribosomes depend on the installation of an unusual {beta}-amino acid, isoaspartate, within the ribosomal protein uS11. In bacteria, mitochondria, and plastids, this modification is catalyzed by the metzincin-like hydrolase YbeY, whereas in archaea and eukaryotes, it is introduced by the atypical kinase Fap7. The formation of this strategically positioned isoaspartate enables correct maturation of the small ribosomal subunit to support protein synthesis and normal cell physiology.

biochemistry↗

bioRxiv2025

Immunogenic Cell Death: the Key to Unlocking the Potential for Combined Radiation and Immunotherapy

Immunogenic cell death (ICD) enhances anti-tumor immunity by releasing tumor-associated antigens and activating the anti-tumor immune system response. However, its potential remains understudied in combination therapies. Here, we develop a mathematical model to quantify the role of ICD in optimizing the efficacy of combined radiotherapy (RT) and macrophage-based immunotherapy. Using preclinical murine data targeting the SIRP-CD47 checkpoint, we show that RT alone induces minimal ICD, whereas disrupting the SIRP-CD47 axis significantly enhances both phagocytosis and systemic immune activation. Our model predicts an optimal RT dose (6-8 Gy) for maximizing ICD, a dose-dependent abscopal effect, and a hierarchy of treatment efficacy, with SIRP-knockout macrophages exhibiting the strongest tumoricidal activity. These findings provide a quantitative framework for designing more effective combination therapies, leveraging ICD to enhance immune checkpoint inhibition and radiotherapy synergy.

cancer biology↗

bioRxiv2023

Mobile retroelements induced by hypomethylating agents are restricted to transpose in myeloid malignancies

Retroelements (RE) present in the human genome are silenced via multiple mechanisms, including DNA methylation, to prevent their potentially mutagenic effect. RE activity, demonstrated by their expression and somatic retrotransposition events, is deregulated in multiple tumor types but not in leukemia. We hypothesized that treatment with hypomethylating agents (HMA), commonly used in myelodysplastic syndromes and acute myeloid leukemia, could lead to increased RE activity and somatic retrotranspositions, and contribute to disease progression. We induced expression of ORF1p protein encoded by long interspersed nuclear element-1 (L1) after 72h treatment with HMA in DAMI and HL-60 cell lines. ORF1p was predominantly localized in the cytoplasm, as evidenced by fluorescent microscopy of the DAMI cell line. To study whether long-term HMA therapy may induce somatic retrotranspositions, we (i) treated both cell lines for four weeks, (ii) analyzed a cohort of 17 MDS patients before and on treatment with HMA. Using a previously established sensitive NGS-based method, no RE events were identified. To conclude, we show that although HMA induces the expression of L1-encoded proteins in tumor myeloid cell lines, de novo somatic retrotransposition events do not arise during the long-term treatment of MDS patients and myeloid cell lines with these agents.

cancer biology↗

bioRxiv2020

Isolation and identification of Phytophthora species on nut-bearing plants

The paper describes the isolation and identification of pathogens from soil samples taken in the Moscow region from walnut plants with signs of wilting and stem ulcers. Isolation of Phytophthora from soil samples was carried out by the method of floating biological baits with subsequent isolation of pathogens on a semi-selective nutrient medium - P5ARP [H]. Samples were taken from the colonies for DNA isolation. After that, PCR analysis was carried out with primers YPh1F / YPh2R and ITS4 / ITS5 and sequencing. As a result of the studies carried out, colonies similar to the morphological characteristics of P. cactorum and P citricola were obtained and confirmed by sequencing.

microbiology↗

bioRxiv2020

Disparities in information on Long-Acting Reversible Contraceptives available to college students on student health center websites in USA

Long Acting Reversible Contraceptive (LARC) methods are among the most effective birth control approaches for adolescent and young adults yet information on these methods is not widespread. We examine LARC information provided by Student Health Centers (SHC) websites from Universities across the USA to document disparities in access to information on these important contraception methods for college students. We find that compared to EC, Condoms, (plus Pap smear as control), LARC is mentioned less frequently than the others and 73% of schools have no LARC content on their SHC websites. There is no standardization in how the sexual and reproductive health information is organized on SHC websites, which might hinder access. When LARC information does exist, readability and accessibility vary. Universities having high rates of the student body who are African American or female are less likely to provide LARC information on their SHC website and universities situated in more rural settings are less likely to post LARC information on their websites.

scientific communication and education↗

bioRxiv2019

YBEY is an essential biogenesis factor for mitochondrial ribosomes

Ribosome biogenesis requires numerous trans-acting factors, some of which are deeply conserved. In Bacteria, the endoribonuclease YbeY is believed to be involved in 16S rRNA 3-end processing and its loss was associated with ribosomal abnormalities. In Eukarya, YBEY appears to generally localize to mitochondria (or chloroplasts). Here we show that the deletion of human YBEY results in a severe respiratory deficiency and morphologically abnormal mitochondria as an apparent consequence of impaired mitochondrial translation. Reduced stability of 12S rRNA and the deficiency of several proteins of the small ribosomal subunit in YBEY knockout cells pointed towards a defect in mitochondrial ribosome biogenesis. The specific interaction of mitoribosomal protein uS11m with YBEY suggests that the latter recruits uS11m to the nascent small subunit in its late assembly stage. This scenario shows similarities with final stages of cytosolic ribosome biogenesis, and may represent a late checkpoint before the mitoribosome engages in translation.

molecular biology↗