Vol 18, No 2 (2026)

Long non-coding RNAs (lncRNAs) are involved in various biological processes, including chromatin modification, cell differentiation, pre-mRNA splicing, translation, etc. Recent studies have revealed that lncRNAs can have a significant impact on the pathogenesis of viral infections by acting as both positive and negative regulators of viral gene expression. This review summarizes the available data on lncRNAs associated with human immunodeficiency virus type 1 (HIV-1). LncRNAs can regulate both the active replication cycle and the latent phase of the HIV-1 infection, during which the integrated proviral DNA remains transcriptionally silent. Moreover, lncRNAs may serve as diagnostic markers and are potential therapeutic targets. A deeper understanding of the intricate interactions between lncRNAs and HIV-1 is essential for developing innovative treatments for the HIV infection and the associated acquired immunodeficiency syndrome (AIDS).

The analysis of protein evolutionary relationships is of both theoretical and practical significance. Identifying and characterizing evolutionary relationships between the components of protein complexes and metabolic enzymes fosters a deeper understanding of their evolutionary history and molecular evolution. The existence of related enzymes makes the annotation of new sequences complicated, since this process relies heavily on accurately determining the protein family classification of the sequence being analyzed. Clusters of Orthologous Groups (COGs) are widely used for the classification of prokaryotic proteins. COGs are constructed based on the occurrence of the respective protein-coding genes within complete genomes. Previously, we introduced COGcollator, a tool designed to visualize the relatedness between COGs by analyzing the hits of their profile HMMs (Hidden Markov Models). This paper presents an update of the COGcollator web service. It is based on the latest version of the COG database and features a completely new interface and additional functionalities. To demonstrate the capabilities of our tool and the validity of the data, we present the COGcollator results for the subunits of NADH:quinone oxidoreductase type 1 (NDH-1), a homologue of the mitochondrial complex I, as the evolutionary relationships of NDH-1 with other protein complexes have been extensively documented in the literature. The web service is available free of charge without registration at https://boabio.belozersky.msu.ru/en/COGcollator. Through the web service interface, users can access pre-calculated COGcollator results for 4,972 COGs and download their respective profile HMMs.

The nonsense-mediated mRNA decay (NMD) pathway is a mRNA quality control mechanism which not only degrades deleterious transcripts but also orchestrates a large number of post-transcriptional regulatory programs through unproductive splicing. We have developed a robust metric derived from splicing quantification in the RNA-seq data to measure NMD efficiency at a sample level. We demonstrate that NMD efficiency varies substantially both between and within tissues, with the magnitude of the variation comparable to that observed upon knockdown of the core NMD factor UPF1. By analyzing TCGA cancer cohorts, we further show that, in many tumors, unproductive splicing events undergo coordinated changes towards either collective suppression or collective activation of NMD isoforms, which is indicative of global deregulation of the activity of the NMD pathway. Consistently, we observed a striking divergence of NMD efficiency in cancers from the tissue-specific baseline level, suggesting that tumors partially erase the NMD signature of their tissue of origin. The application of the developed metric to RNA-binding protein knockdowns made it possible to identify several novel potential regulators of NMD efficiency. In sum, this study provides a solid framework for quantifying NMD efficiency, describes its biological and clinical relevance, and opens new avenues for dissecting mechanisms of post-transcriptional gene expression regulation by the NMD pathway.

Genital lichen sclerosus (GLS) is a chronic inflammatory dermatosis that affects the genital skin. Despite different clinical manifestations, the pathogenesis of GLS in men and women is believed to be common and is attributed to a combination of autoimmune and genetic factors. In this study, we compared the transcriptomic profiles of penile (mGLS) and vulvar lichen sclerosus (VLS), aiming to identify commonly deregulated genes. We observed a substantial heterogeneity in the transcriptomic signatures in mGLS samples, which is driven by different compositions of immune infiltrates. In mGLS, gene expression signatures strongly indicate epidermis dysfunction and overexpression of the epithelial inflammation marker Keratin 6 (KRT6) and chitinase CHIT1. No significant changes in the expression levels of known GLS markers, such as VIM, CTNNB1, LGALS7 and ECM1, were detected. However, significant changes in the expression levels of the genes associated with autoimmune diseases and the genes upregulated in squamous cell carcinoma, including TNF, CCNB1 and RUNX3, were observed. There was no enrichment in the polyU/UC insertions that were reported previously. Instead, we have identified a long non-coding RNA DRAIC with a high coding potential that is commonly upregulated in mGLS and VLS. Taken together, our results provide a comprehensive picture of the shared transcriptomic signatures, including novel biomarkers and potential therapeutic targets.

Genetic variation in the genes involved in the maintenance of cellular homeostasis may influence susceptibility to type 2 diabetes (T2D). However, the nature of the interplay among these loci and their prognostic value remains unclear. In this study, we analyzed variants in the FOXO3A, FOXO3, FOXO1, HMOX1, and SIRT1 genes. The HMOX1 rs2071746*T/T genotype was associated with an increased risk of T2D (OR = 1.36, P_FDR = 0.030), whereas the FOXO1 rs9549240 (OR = 0.52, P_FDR = 0.002) and SIRT1 rs3758391 (OR = 0.80, P_FDR = 0.015) genotypes exhibited a protective effect. We detected nonlinear interactions, including FOXO1 rs9549240*G + SIRT1 rs3758391*T + SIRT1 rs7895833*A and HMOX1 rs2071746*A + SIRT1 rs3758391*T + SIRT1 rs7895833*A, with significant synergistic effects (SF = 3.19 and 2.56, P < 0.03). Models incorporating these interactions achieved an AUC of 69.8%, which increased to 86.2% when combined with age, sex, and the body mass index. These findings suggest that interactions between the pathways regulating oxidative stress and metabolism may contribute to the genetic predisposition to T2D.

Persistence – i.e., the ability to exist in a metabolically inactive form – allows bacteria to accumulate genetic advantages. The evolution of the pathogenic potential of Klebsiella pneumoniae has led to the emergence of strains simultaneously characterized by increased aggressiveness (virulence) and prolonged survival in the host organism. This combination of properties contributes to the emergence of “superbugs,” necessitating the search for specific markers that would make it possible to prevent the spread of highly adaptive clones. Hypervirulent K. pneumoniae (hvKp) strains represent a growing global health threat, since they combine high invasiveness and antibiotic resistance. An analysis of 92 K. pneumoniae clinical isolates was conducted to assess the prevalence of the key hypervirulence genes (iroB, peg-344, rmpA, rmpA2, and iucA) and investigate their association with the bacterial persister formation gene ptsH. It was found that 64.1% (59/92) of the isolates carried at least one hvKp gene, iucA being the most frequent one (62.0%). The full set of five hvKp genes was identified in only one case (1%). The strains of sequence types ST23, ST268, ST86, ST534, ST219, ST101, and ST395 accumulated virulence genes, whereas ST512 and ST14 rarely harbored hvKp genes. A key finding was the detection of a significant association between the presence of the ptsH gene (found in 50% of the strains) and the accumulation of hvKp genes: the ptsH-positive strains were statistically more likely to harbor the complete aerobactin operon (iucABCD), in combination with one or more additional hypervirulence genes, compared to the ptsH-negative strains (p < 0.05). Our findings indicate that the ptsH gene is crucial in the formation of polygenically determined hypervirulence, and that its role in controlling bacterial persistence creates evolutionary advantages under stress induced by antibiotics or immune factors, thus promoting evasion of their actions. The phosphotransferase system (PTS), to which the ptsH gene belongs, can potentially become a novel source of molecular targets for the therapy of infections caused by hypervirulent K. pneumoniae strains.