Search Results (91)

Capsicum annuum (pepper) is a globally significant Solanaceous crop vulnerable to devastating pathogens such as Phytophthora capsici. Nucleotide-binding leucine-rich repeat (NLRs) proteins are crucial intracellular immune receptors mediating effector-triggered immunity (ETI). This study presents the comprehensive genome-wide identification and analysis of the NLR gene family in pepper using the high-quality ‘Zhangshugang’ reference genome. We identified 288 high-confidence canonical NLR genes. Chromosomal distribution analysis showed significant clustering, particularly near telomeric regions, with Chr09 harboring the highest density (63 NLRs). Evolutionary analysis demonstrated that tandem duplication is the primary driver of NLR family expansion, accounting for 18.4% of NLR genes (53/288), predominantly on Chr08 and Chr09. Analysis of promoter cis-regulatory elements (CREs) revealed enrichment in defense-related motifs, with 82.6% of promoters (238 genes) containing binding sites for salicylic acid (SA) and/or jasmonic acid (JA) signaling. Transcriptome profiling of Phytophthora capsici-infected resistant (C. annuum cv. CM334) and susceptible (C. annuum cv. NMCA10399) cultivars identified 44 significantly differentially expressed NLR genes, and protein–protein interaction (PPI) network analysis predicted key interactions among them, with Caz01g22900 and Caz09g03820 as potential hubs. This study elucidates the tandem-duplication-driven expansion, domain-specific functional implications, and expression dynamics of the pepper NLR family. It identifies conserved and lineage-specific candidate NLR genes, including Caz03g40070, Caz09g03770, Caz10g20900, and Caz10g21150. These findings provide valuable candidate gene targets for the development of molecular markers for pepper resistance to Phytophthora capsici. Full article

Acute myeloid leukemia (AML) is a malignant hematological tumor with a high prevalence in elderly people, and circular RNA (circRNA) plays an important role in age-related diseases. Induction of cancer cell senescence is a highly promising therapeutic strategy; however, the presence of senescence-associated circRNAs in AML remains to be elucidated. Here, we show that the expression patterns of circRNAs differed between elderly AML patients and healthy volunteers. circSATB1 was significantly overexpressed in elderly patients and AML cells. Knockdown of circSATB1 resulted in the inhibition of proliferation and arrest of the cell cycle in the G0/G1 phase; no effect on apoptosis or DNA integrity was observed, and precocious cellular senescence was promoted, characterized by no change in telomere length. Database analysis revealed that there may be two miRNA and nine RNA-binding proteins (RBPs) involved in regulating the cellular functions of circSATB1. Our observations uncover circSATB1-orchestrated cell senescence in AML, which provides clues for finding more modest therapeutic targets for AML. Full article

The phosphatidylethanolamine-binding protein (PEBP) gene family is critical for regulating plant growth, development, and flowering. Sunflower (Helianthus annuus L.) is the fourth most important oilseed crop globally. However, the genomic structure and functional diversity of PEBP genes in sunflower remain unexplored. Leveraging the recently assembled telomere-to-telomere (T2T) sunflower genome, a genome-wide analysis of the HaPEBP family was carried out. A total of 12 PEBP genes were identified in sunflower and categorized into three subfamilies: TFL1-like, FT-like, and MFT-like. Phylogenetic and synteny analyses revealed that tandem duplication events have substantially contributed to the evolution and expansion of the HaPEBP gene family. Furthermore, the analysis of the promoter regions revealed 77 distinct cis-acting elements, including 35 related to light signaling and growth regulation, highlighting their potential involvement in the regulation of flowering and development in sunflower. Expression profile analysis using RNA-seq data across various tissues indicated that FT-like and TFL1-like HaPEBP genes may be the key regulators of flowering time and plant architecture in sunflower varieties. This study offers valuable insights into the structural, evolutional, and functional dynamics of the HaPEBP gene family and holds significant implications for sunflower breeding strategies aimed at optimizing flowering time and plant architecture traits. Full article

Elevated levels of reactive oxygen species (ROS) are caused by ultraviolet B radiation (UV-B) stress. In response, plants strengthen their cell membranes, impeding photosynthesis. Additionally, UV-B stress initiates oxidative stress within the antioxidant defense system and alters secondary metabolism, particularly by increasing the quantity of UV-absorbing compounds such as flavonoids. The v-myb avian myeloblastosis viral oncogene homolog (MYB) transcription factor (TF) may participate in a plant’s response to UV-B damage through its regulation of flavonoid biosynthesis. In this study, we discovered that the photosynthetic activity of Rhododendron chrysanthum Pall. (R. chrysanthum) decreased when assessing parameters of chlorophyll (PSII) fluorescence parameters under UV-B stress. Concurrently, antioxidant system enzyme expression increased under UV-B exposure. A multi-omics data analysis revealed that acetylation at the K68 site of the RcTRP5 (telomeric repeat binding protein of Rhododendron chrysanthum Pall.) transcription factor was upregulated. This acetylation modification of RcTRP5 activates the antioxidant enzyme system, leading to elevated expression levels of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT). Upregulation is also observed at the K95 site of the chalcone isomerase (CHI) enzyme and the K178 site of the anthocyanidin synthase (ANS) enzyme. We hypothesize that RcTRP5 influences acetylation modifications of CHI and ANS in flavonoid biosynthesis, thereby indirectly regulating flavonoid production. This study demonstrates that R. chrysanthum can be protected from UV-B stress by accumulating flavonoids. This could serve as a useful strategy for enhancing the plant’s flavonoid content and provide a valuable reference for research on the metabolic regulation mechanisms of other secondary substances. Full article

Iron–sulfur (Fe-S) clusters are essential cofactors found in many proteins in the mitochondria, cytosol, and nucleus of the cell. These versatile cofactors may undergo reversible oxidation–reduction reactions to enable electron transfers; they may be structural and confer stability to a folded protein; they may be regulatory and transduce an iron signal that alters the function or stability of a recipient protein. Of the nearly 70 proteins described in mammalian cells that bind Fe-S clusters, about half localize exclusively or partially to the nucleus, where they are required for DNA replication and repair, telomere maintenance, transcription, mitosis, and cell cycle control. Most nuclear Fe-S cluster proteins interact with DNA, including DNA polymerases, primase, helicases, and glycosylases. However, the specific roles of the clusters in the enzymatic activities of these proteins and their interplay with DNA remain a matter of debate. Defects in the metallation of nuclear Fe-S proteins cause genome instability and alter the regulation of cell division and proliferation, which are hallmarks of various genetic diseases and cancers. Here, we provide an inventory of the nuclear Fe-S cluster-binding proteins and discuss cluster types, binding sites, the process of cluster acquisition, and the potential roles of the cluster in the function of the proteins. However, many questions remain unresolved. We highlight critical gaps in our understanding of cluster delivery to nuclear client proteins, the potential for cluster repair, and the mechanistic roles that clusters play in these enzymes. Taken together, this review brings the focus to the nucleus of the human cell as a hotspot for Fe-S cluster proteins and aims to inspire new research on the roles of iron in DNA metabolism and the maintenance of genome integrity. Full article

Skin is a crucial organ for preserving the body’s equilibrium. Like other parts of the body, skin also ages due to extrinsic and intrinsic factors, leading to several signs such as wrinkles, spots, and a decline in elasticity, causing a range of issues similar to those seen elsewhere in the body. Some of these factors include ultraviolet (UV) radiation, hormonal disorders, genetic factors, loss of moisture, metabolic disorders, exposure to chemicals, and smoking. Colostrum, which is the initial foremilk, has shown positive effects on the consequences of these factors. Its content is richer than mature milk and contains several beneficial components. For instance, it includes hyaluronic acid, a molecule that binds water and keeps the skin hydrated; lactoferrin, with high antimicrobial properties; immunoglobulins, which are responsible for immunity; growth factors, which increase the amount of collagen, the main protein type of the skin; and, finally, the telomerase enzyme, which maintains the telomere’s length and, thus, decelerates the aging process. It has recently become apparent that using skin products with natural ingredients is essential. Considering its nature, contents, and effects, colostrum stands out as an excellent material for the cosmetic industry, especially for the aging sector. Therefore, the aim of this review article is to demonstrate the potential application of natural colostrum in skin health and its usage in natural cosmetic products in the cosmetic sector. Full article

Telomerase is an enzyme involved in the maintenance of telomeres. Telomere shortening due to the end-replication problem is a threat to the genome integrity of all eukaryotes. Telomerase inside cells depends on a myriad of protein–protein and RNA–protein interactions to properly assemble and regulate the function of the telomerase holoenzyme. These interactions are well studied in model eukaryotes, like humans, yeast, and the ciliated protozoan known as Tetrahymena thermophila. Emerging evidence also suggests that deep-branching eukaryotes, such as the parasitic protist Trypanosoma brucei require conserved and novel RNA-binding proteins for the assembly and function of their telomerase. In this review, we will discuss telomerase regulatory pathways in the context of telomerase-interacting proteins, with special attention paid to RNA-binding proteins. We will discuss these interactors on an evolutionary scale, from parasitic protists to humans, to provide a broader perspective on the extensive role that protein–protein and RNA–protein interactions play in regulating telomerase activity in eukaryotes. Full article

We used a replicative lifespan (RLS) experiment of K6001 yeast to screen for anti-aging compounds within lavender extract (Lavandula angustifolia Mill.), leading to the discovery of β-cyclocitral (CYC) as a potential anti-aging compound. Concurrently, the chronological lifespan (CLS) of YOM36 yeast and mammalian cells confirmed the anti-aging effect of CYC. This molecule extended the yeast lifespan and inhibited etoposide (ETO)-induced cell senescence. To understand the mechanism of CYC, we analyzed its effects on telomeres, oxidative stress, and autophagy. CYC administration resulted in notable increases in the telomerase content, telomere length, and the expression of the telomeric shelterin protein components telomeric-repeat binding factor 2 (TRF2) and repressor activator protein 1 (RAP1). More interestingly, CYC reversed H₂O₂-induced telomere damage and exhibited strong antioxidant capacity. Moreover, CYC improved the survival rate of BY4741 yeast under oxidative stress induced by 6.2 mM H₂O₂, increasing the antioxidant enzyme activity while reducing the reactive oxygen species (ROS), reactive nitrogen species (RNS), and malondialdehyde (MDA) levels. Additionally, CYC enhanced autophagic flux and free green fluorescent protein (GFP) expression in the YOM38-GFP-ATG8 yeast strain. However, CYC did not extend the RLS of K6001 yeast mutants, such as Δsod1, Δsod2, Δcat, Δgpx, Δatg2, and Δatg32, which lack antioxidant enzymes or autophagy-related genes. These findings reveal that CYC acts as an anti-aging agent by modifying telomeres, oxidative stress, and autophagy. It is a promising compound with potential anti-aging effects and warrants further study. Full article

Telomeres act as the protective caps of eukaryotic linear chromosomes; thus, proper telomere maintenance is crucial for genome stability. Successful telomere replication is a cornerstone of telomere length regulation, but this process can be fraught due to the many intrinsic challenges telomeres pose to the replication machinery. In addition to the famous “end replication” problem due to the discontinuous nature of lagging strand synthesis, telomeres require various telomere-specific steps for maintaining the proper 3′ overhang length. Bulk telomere replication also encounters its own difficulties as telomeres are prone to various forms of replication roadblocks. These roadblocks can result in an increase in replication stress that can cause replication forks to slow, stall, or become reversed. Ultimately, this leads to excess single-stranded DNA (ssDNA) that needs to be managed and protected for replication to continue and to prevent DNA damage and genome instability. RPA and CST are single-stranded DNA-binding protein complexes that play key roles in performing this task and help stabilize stalled forks for continued replication. The interplay between RPA and CST, their functions at telomeres during replication, and their specialized features for helping overcome replication stress at telomeres are the focus of this review. Full article

Seryl-tRNA synthetases (SerRSs), members of the aminoacyl-tRNA synthetase family, interact with diverse proteins, enabling SerRSs to enhance their role in the translation of the genetic message or to perform alternative functions in cellular processes beyond translation. Atypical archaeal SerRS interacts with arginyl-tRNA synthetase and proteins of the ribosomal P-stalk to optimize translation through tRNA channeling. The complex between yeast SerRS and peroxin Pex21p provides a connection between translation and peroxisome function. The partnership between Arabidopsis SerRS and BEN1 indicates a link between translation and brassinosteroid metabolism and may be relevant in plant stress response mechanisms. In Drosophila, the unusual heterodimeric mitochondrial SerRS coordinates mitochondrial translation and replication via interaction with LON protease. Evolutionarily conserved interactions of yeast and human SerRSs with m³C32 tRNA methyltransferases indicate coordination between tRNA modification and aminoacylation in the cytosol and mitochondria. Human cytosolic SerRS is a cellular hub protein connecting translation to vascular development, angiogenesis, lipogenesis, and telomere maintenance. When translocated to the nucleus, SerRS acts as a master negative regulator of VEGFA gene expression. SerRS alone or in complex with YY1 and SIRT2 competes with activating transcription factors NFκB1 and c-Myc, resulting in balanced VEGFA expression important for proper vascular development and angiogenesis. In hypoxia, SerRS phosphorylation diminishes its binding to the VEGFA promoter, while the lack of nutrients triggers SerRS glycosylation, reducing its nuclear localization. Additionally, SerRS binds telomeric DNA and cooperates with the shelterin protein POT1 to regulate telomere length and cellular senescence. As an antitumor and antiangiogenic factor, human cytosolic SerRS appears to be a promising drug target and therapeutic agent for treating cancer, cardiovascular diseases, and possibly obesity and aging. Full article

It has been more than three decades since the discovery of multifunctional factors, the Non-POU-Domain-Containing Octamer-Binding Protein, NonO, and the Splicing Factor Proline- and Glutamine-Rich, SFPQ. Some of their functions, including their participation in transcriptional and posttranscriptional regulation as well as their contribution to paraspeckle subnuclear body organization, have been well documented. In this review, we focus on several other established roles of NonO and SFPQ, including their participation in the cell cycle, nonhomologous end-joining (NHEJ), homologous recombination (HR), telomere stability, childhood birth defects and cancer. In each of these contexts, the absence or malfunction of either or both NonO and SFPQ leads to either genome instability, tumor development or mental impairment. Full article

Telomeres are nucleoprotein complexes that cap the ends of eukaryotic linear chromosomes. Telomeric DNA is bound by shelterin protein complex to prevent telomeric chromosome ends from being recognized as damaged sites for abnormal repair. To overcome the end replication problem, cancer cells mostly preserve their telomeres by reactivating telomerase, but a minority (10–15%) of cancer cells use a homologous recombination-based pathway called alternative lengthening of telomeres (ALT). Recent studies have found that shelterin components play an important role in the ALT mechanism. The binding of TRF1, TRF2, and RAP1 to telomeres attenuates ALT activation, while the maintenance of ALT telomere requires TRF1 and TRF2. POT1 and TPP1 can also influence the occurrence of ALT. The elucidation of how shelterin regulates the initiation of ALT remains elusive. This review presents a comprehensive overview of the current findings on the regulation of ALT by shelterin components, aiming to enhance the insight into the altered functions of shelterin components in ALT cells and to identify potential targets for the treatment of ALT tumor cells. Full article

Oxidative stress and impaired mitophagy are the hallmarks of cardiomyocyte senescence. Specifically, a decrease in mitophagic flux leads to the accumulation of damaged mitochondria and the development of senescence through increased ROS and other mediators. In this study, we describe the preventive role of A5⁺, a mix of polyphenols and other micronutrients, in doxorubicin (DOXO)-induced senescence of H9C2 cells. Specifically, H9C2 cells exposed to DOXO showed an increase in the protein expression proteins of senescence-associated genes, p21 and p16, and a decrease in the telomere binding factors TRF1 and TRF2, indicative of senescence induction. Nevertheless, A5⁺ pre-treatment attenuated the senescent-like cell phenotype, as evidenced by inhibition of all senescent markers and a decrease in SA-β-gal staining in DOXO-treated H9C2 cells. Importantly, A5⁺ restored the LC3 II/LC3 I ratio, Parkin and BNIP3 expression, therefore rescuing mitophagy, and decreased ROS production. Further, A5⁺ pre-treatment determined a ripolarization of the mitochondrial membrane and improved basal respiration. A5⁺-mediated protective effects might be related to its ability to activate mitochondrial SIRT3 in synergy with other micronutrients, but in contrast with SIRT4 activation. Accordingly, SIRT4 knockdown in H9C2 cells further increased MnSOD activity, enhanced mitophagy, and reduced ROS generation following A5⁺ pre-treatment and DOXO exposure compared to WT cells. Indeed, we demonstrated that A5⁺ protects H9C2 cells from DOXO-induced senescence, establishing a new specific role for A5⁺ in controlling mitochondrial quality control by restoring SIRT3 activity and mitophagy, which provided a molecular basis for the development of therapeutic strategies against cardiomyocyte senescence. Full article

The MYB (v-Myb avivan myoblastsis virus oncogene homolog) transcription factor family is one of the largest families of plant transcription factors which plays a vital role in many aspects of plant growth and development. MYB-related is a subclass of the MYB family. Fifty-nine Arabidopsis thaliana MYB-related (AtMYB-related) genes have been identified. In order to understand the functions of these genes, in this review, the promoters of AtMYB-related genes were analyzed by means of bioinformatics, and the progress of research into the functions of these genes has been described. The main functions of these AtMYB-related genes are light response and circadian rhythm regulation, root hair and trichome development, telomere DNA binding, and hormone response. From an analysis of cis-acting elements, it was found that the promoters of these genes contained light-responsive elements and plant hormone response elements. Most genes contained elements related to drought, low temperature, and defense and stress responses. These analyses suggest that AtMYB-related genes may be involved in A. thaliana growth and development, and environmental adaptation through plant hormone pathways. However, the functions of many genes do not occur independently but instead interact with each other through different pathways. In the future, the study of the role of the gene in different pathways will be conducive to a comprehensive understanding of the function of the gene. Therefore, gene cloning and protein functional analyses can be subsequently used to understand the regulatory mechanisms of AtMYB-related genes in the interaction of multiple signal pathways. This review provides theoretical guidance for the follow-up study of plant MYB-related genes. Full article

Oxidative stress (OS) and inflammation are features of metabolic syndrome (MetS) that can contribute to the shortening of telomere length (TL), a marker of cellular ageing. Research indicates that exercise can positively influence MetS-associated conditions and TL. However, the effects of low-volume exercise types on TL are still unknown. We investigated the impact of very-low-volume high-intensity interval training (LV-HIIT), one-set resistance training (1-RT), and whole-body electromyostimulation (WB-EMS) on TL, inflammation, and cardiometabolic indices in 167 MetS patients. Data were derived from two randomized controlled trials where patients were allocated to an exercise group (2 sessions/week, for 12 weeks) or a control group. All groups received standard-care nutritional weight loss counselling. TL was determined as the T/S ratio (telomere to single-copy gene amount). All groups significantly reduced body weight (p < 0.05), but the T/S-ratio (p < 0.001) only increased with LV-HIIT. OS-related inflammatory markers (C-reactive protein, interleukin-6, and lipopolysaccharide-binding protein) only decreased (p < 0.05) following LV-HIIT. The MetS severity z-score improved with LV-HIIT (p < 0.001) and 1-RT (p = 0.014) but not with WB-EMS. In conclusion, very-low-volume exercise modalities have differential effects on telomeres, inflammation, and cardiometabolic health. Only LV-HIIT but not strength-based low-volume exercise increased TL in MetS patients, presumably due to superior effects on OS-related inflammatory markers. Full article