Biology subjects

Smirnova, E.

Publications and source records attributed to Smirnova, E..

4 recordsLinked to original sources

bioRxiv2025

In harmony? A scoping review of methods to combine multiple 16S amplicon data sets

Robust evidence on relationships between the human microbiome and health are critical for understanding and improving the human condition. However, there is little information about methodological approaches to combine and analyze multiple microbiome data sets. To address this gap, we conducted a scoping review of studies that combine sequencing data from multiple data sets to understand the study objectives, data sources and selection, feature -table assembly methods, and analyses. References were identified through a systematic search of literature published between 2011 and 2022. Our final review included 60 articles. Despite the wide-spread use of the word "meta-analysis," we found that only 24 studies used a systematic process to select their data sets, suggesting multiple meanings of the term within the field. While more than two thirds of studies used at least one publicly available data source, 19 had to request data from the original authors. Most studies (60%) combined data sets from multiple disjoint hypervariable regions. The number of hypervariable regions combined was not associated with the table construction method, but feature table construction method and the number of hypervariable regions influenced analytical resolution. Our results suggest the microbiome community needs to examine the use of terminology and analytic approaches for combining data sets; that additional work is needed to explore the impact of data source on bias in combined studies; and invite an independent evaluation of the methods used for feature table construction across disjoint regions.

microbiology↗

bioRxiv2023

Binding to nucleosome poises SIRT6 for histone H3 de-acetylation

Sirtuin 6 (SIRT6) is an NAD+ dependent histone H3 deacetylase that is prominently found associated with chromatin, attenuates transcriptionally active promoters and regulates DNA repair, metabolic homeostasis and lifespan. Unlike other sirtuins, it has low affinity to free histone tails but demonstrates strong binding to nucleosomes. It is poorly understood how SIRT6 docking on nucleosomes stimulates its histone deacetylation activity. Here we present the structure of human SIRT6 bound to a nucleosome determined by cryogenic electron microscopy. The zinc finger domain of SIRT6 associates tightly with the acidic patch of the nucleosome through multiple arginine anchors. The Rossmann fold domain binds to the terminus of the looser DNA half of the nucleosome, detaching two turns of the DNA from the histone octamer and placing the NAD+ binding pocket close to the DNA exit site. This domain shows flexibility with respect to the fixed zinc finger and moves with, but also relative to, the unwrapped DNA terminus. We apply molecular dynamics simulations of the histone tails in the nucleosome to show that in this mode of interaction, the active site of SIRT6 is perfectly poised to catalyze deacetylation of the H3 histone tail and that the partial unwrapping of the DNA allows even lysines close to the H3 core to reach the enzyme.

molecular biology↗

bioRxiv2021

Molecular features of RNA silencing against phloem-restricted polerovirus TuYV enable amplification of silencing signal from host transcripts

In plants and some animal lineages, RNA silencing is an efficient and adaptable defense mechanism against viruses. To counter it, viruses encode suppressor proteins that interfere with RNA silencing. Phloem-restricted viruses are spreading at an alarming rate and cause substantial reduction of crop yield, but how they interact with their hosts at the molecular level is still insufficiently understood. Here, we investigate the antiviral response against phloem-restricted turnip yellows virus (TuYV) in the model plant Arabidopsis thaliana. Using a combination of genetics, deep sequencing, and mechanical vasculature enrichment, we show that the main axis of silencing active against TuYV involves 22-nt vsiRNA production by DCL2, and their preferential loading into AGO1. Unexpectedly, and despite the viral encoded VSR P0 previously shown to mediate degradation of AGO proteins, vascular AGO1 undergoes specific post-translational stabilization during TuYV infection. We also identify vascular novel secondary siRNA produced from conserved plant transcripts and initiated by DCL2-processed AGO1-loaded vsiRNA, supporting a viral strategy to modulate host response. Collectively, our work uncovers the complexity of antiviral RNA silencing against phloem-restricted TuYV and prompts a re-assessment of the role of its suppressor of silencing P0 during genuine infection.

plant biology↗

bioRxiv2019

Stress- and pathway-specific impacts of impaired jasmonoyl-isoleucine (JA-Ile) catabolism on defense signaling and biotic stress resistance in Arabidopsis

Jasmonate (JA) synthesis and signaling are essential for plant defense upregulation upon herbivore or microbial attacks. Stress-induced accumulation of jasmonoyl-isoleucine (JA-Ile), the bioactive hormonal form triggering major transcriptional changes, is often dynamic and transient, due to the existence of potent removal mechanisms. Two distinct but interconnected JA-Ile turnover pathways have been described in Arabidopsis, either via cytochrome P450 (CYP94)-mediated oxidation, or through deconjugation by the amidohydrolases (AH) IAR3 and ILL6. Their impact was not well known because of gene redundancy and compensation mechanisms when each pathway was partially impaired. Here we address the consequences of fully blocking either or both pathways on JA homeostasis and defense signaling in three mutant backgrounds: a double iar3 ill6 (2ah) mutant, a triple cyp94b1 b3 c1 mutant (3cyp), and a newly generated quintuple (5ko) mutant deficient in all known JA-Ile-degrading activities. These lines behaved very differently in response to either mechanical wounding, insect attack or fungal infection, highlighting the stress-specific contributions and impacts of JA-Ile catabolic pathways. Deconjugation and oxidative pathways contributed additively to JA-Ile removal upon wounding, but their genetic impairement had opposite impacts on Spodoptera littoralis larvae feeding: 2ah line was more resistant whereas 3cyp was more susceptible to insect attack. In contrast, 2ah, 5ko but not 3cyp overaccumulated JA-Ile upon inoculation by Botrytis cinerea, yet 3cyp was most resistant to the fungus. Despite of building-up unprecedented JA-Ile levels, 5ko displayed near WT levels of resistance in both bioassays. Molecular and metabolic analysis indicated that restrained JA-Ile catabolism resulted in enhanced defense and resistance levels only if genes encoding JAZ or JAM negative regulators were not simultaneously overstimulated. Our data demonstrate that despite of acting on a shared hormonal substrate, AH or/and CYP94 deficiency differentially impacts JA homeostasis, responses and tolerance to related biotic stresses.

plant biology↗