The Polycomb Group (PcG) system controls developmental transitions and cell states across species. Two main PcG complexes, Polycomb Repressive Complexes 1 and 2 (PRC1, PRC2), regulate transcription and form epigenetic memory through chromatin. Polyhomeotic (Ph) is an essential PRC1 subunit that has received relatively little attention, perhaps because it is not implicated in either depositing or recognizing histone post-translational modifications (PTMs). Instead, Ph regulates chromatin architecture through its hallmark polymerizing sterile alpha motif (SAM). Here we review the biochemistry and function of Ph and mammalian polyhomeotic-like proteins (PHCs). We describe the role of SAM polymerization and evidence for essential polymerization-independent SAM functions. The evolutionary origins of Ph and possible co-evolution of disordered and ordered regions to maintain but modify Ph function are considered. Finally, we draw parallels between SAM function in animals and a recently discovered polymerization activity in a plant PcG protein that may reflect convergent evolution.
Telomeres in epithelial tumors are maintained by telomerase; however, in the MDA-MB-231 breast cancer cell line, treated by doxorubicin (DOX), we found a transient suppression of the telomerase (TERT) before cell growth resumed. Accumulation of cells in late-S-G2/M, mitotic slippage, octaploidy, and decrease of lamin B1 (LMNB1) coincided with this response. The telomere clustering and ALT-like process marked by the telomere shelterin (TRF2) colocalised in PML bodies with DNA DSBs (γH2AX) and recombinase RAD51 were observed in 11-12% of cells. They were preset by arrays of PML-bodies juxta-colocalized with the foci of meiotic prophase proteins SPO11 and DMC1. On the 3rd week, the cells de-polyploidised and returned to the normal cycle, telomerase, and mitosis. ALT-like bodies were also found in BRAFV600E-SK-MEL-28 DOX-treated melanoma cells. However, after sublethal doses of DOX, the formation of PML dimeric rods flanked and tandemly joined by misrepaired TRF2/γH2AX foci occured. Such PML tracts, circumventing cell nuclei undergoing MOS-microtubule-driven rotation, interacted with peripheral chromatin and intermitted with LMNB1 fragments. Furthermore, LMNB1 massively left the nuclear periphery, forming intranuclear flows, and/or convoluted into large peri-nucleolar PML bodies. We interpret our observations as the attempts by damaged, senescing cancer cells to use several mechanisms exploiting PML isoforms and meiotic proteins for telomere repair.
Aging leads to a progressive loss of muscle mass and strength, termed sarcopenia, which is accelerated by inactivity and exacerbated by intrinsic cellular and molecular dysfunctions within the muscle fiber. Central to these changes is mechanotransduction, the process by which mechanical stimuli are converted into biochemical cues critical for protein synthesis, cytoskeletal remodeling, calcium signaling, and metabolism. Recent evidence highlights the nucleus as a key mechanosensory organelle in skeletal muscle. Forces transmitted from the extracellular matrix (ECM) through the cytoskeleton reach the nuclear envelope, where the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex and nuclear lamina convert physical stress into gene-regulatory events. Aging may alter these structures, producing changes in nuclear morphology, decreased stiffness, envelope fragility, and compromised transcriptional control. This review examines how the ECM, cytoskeleton, LINC complex, and nuclear lamina change in aged skeletal muscle, proposing that impaired nuclear mechanosignaling contributes to muscle fiber dysfunction during physiological aging.
Cuscuta janarthanamii Kolte, A. Deshp. Kambale, a recently described species, has been investigated for its chromosomal behaviour. This study reveals the presence of holocentric chromosomes and inverted meiosis in the species. This behaviour was confirmed with four distinct observations, namely the presence of an additional supernumerary chromosome during meiotic metaphase, parallel alignment of chromosomes to the equatorial plate, their movement in the same orientation towards poles and formation of bivalents of non-sister chromatids during meiotic anaphase-1. Collectively, these observations confirm that C. janarthanamii undergoes inverted meiosis, a phenomenon that may be linked to the adaptation of the species under environmental stress conditions. This article aligns with SDG 15 (Life on Land) of the UN Agenda for Sustainable Development.
Natural selection shapes the genome by favoring beneficial mutations, leading to selective sweeps through the hitchhiking effect. Identification of such sweeps provides valuable insights into genomic regions influencing adaptation and economically important traits. The present study was aimed to characterize hard and soft selective sweeps in Karan Fries (KF) cattle developed from crossing Holstein Friesian (HF) and Tharparkar (TH). A haplotype frequency spectrum-based approach using the T-statistics was employed to detect selective sweep signatures across the genome. KF exhibited a markedly higher number of hard sweeps (491) compared to HF (183) and TH (136), whereas the number of soft sweeps was comparable among the three breeds. The elevated hard sweep count in KF reflects rapid fixation of novel allelic combinations generated by Bos taurus and Bos indicus admixture under nine generations of intense artificial selection, producing a functionally heterogeneous hub-gene network spanning reproductive (GAS8), genome-maintenance (EXO1, ERCC1), and immune-regulatory (DBNDD1, DEF8) axes rather than converging on a single pathway as in the parental breeds. HF hard sweep hub genes (POLR2E, RPL19, EIF4A3) converged on ribosome biogenesis supporting lactational protein synthesis, while TH hub genes (GABRA4, GABRA5, GABRB1, GABRB3, GABRG3, IFNAR1) reflected tropical neurological and reproductive adaptation. Soft sweep hub genes across breeds converged on ribosomal and mitochondrial ribosomal proteins (KF: MED1, MRPL16, MRPL22; HF: RACK1, RPL27A, MRPS11; TH: MRPL1, MRPS12, MRPL24), indicating shared polygenic selection on translational efficiency. QTL analysis identified milk production as the dominant trait category. These findings offer candidate loci for customized genomic selection panels supporting sustainable tropical dairy production. This article aligns with SDG 2 (Zero Hunger) of the UN Agenda for Sustainable Development.
Iron deficiency, impacting more than half of the global population, poses a major health concern and contributing factor for malnutrition worldwide. Maize serves as the staple food in many parts of the world, while it is also a predominant component of animal feed. However, maize grains of traditional cultivars lack adequate levels of iron, thereby making them poor in nutrition. Developing iron-rich maize is therefore crucial to combat hidden hunger and boost global nutrition status. The gene, NAC78, is reported to be involved in the accumulation of kernel iron in temperate maize genotypes. The present investigation involved analysing the associated variation in NAC78 among a set of 96 sub-tropically adapted diverse maize genotypes. Two breeder-friendly haplotype-linked markers were developed (AS-PCR and dCAPS) along with an InDel marker to track the polymorphism individually. Two extreme haplotypes were identified in sub-tropically adapted maize genotypes based on promoter polymorphisms: ‘Hap1’ had SNPs C (− 371 bp), T (− 366 bp), T (− 330 bp), and no deletion (42 bp); and ‘Hap2’ possessed SNPs T (− 371 bp), C (− 366 bp), G (− 330 bp), and deletion (42 bp). ‘Hap1’ was observed in 52.1
Chromosomal rearrangements are a major cause of human disorders. They can be numerical or structural abnormalities, and understanding their frequency and nature is vital for accurate diagnosis and genetic counselling. Despite the widespread adoption of sequencing technologies, conventional cytogenetics remains indispensable for detecting balanced and complex rearrangements that often escape array- and sequencing-based approaches. In this study, we combined long-term cytogenetic surveillance with targeted molecular analyses and genome sequencing to characterise the spectrum of chromosomal abnormalities in Southern India and to resolve a novel disease-associated rearrangement. A retrospective analysis of 24,633 cases (1998–2024) was performed using G-banding, C-banding, Ag-NOR staining, FISH, chromosomal microarray, and genome sequencing. In all cases, karyotyping was performed, but FISH/CMA/sequencing was performed in selected cases based on clinical indication. Chromosomal abnormalities were detected in 1,721 (6.9
Kodo millet (Paspalum scrobiculatum L.) is a nutrient-rich and climate-resilient crop. Its productivity is often constrained by strong genotype × environment (G × E) interactions and lodging susceptibility, necessitating the need for identifying stable performing cultivars for yield and non-lodging traits. In this study, 36 mutants along with the CO 3, from which mutants were generated, and four checks (ATL 1, ATL 2, ATL 4, and TNAU 86) were evaluated across environments for photosynthetic efficiency, culm strength, and single plant yield using AMMI, GGE, MGIDI, and MTSI models. The joint ANOVA revealed significant G × E effects for all traits. For photosynthetic efficiency, AMMI and GGE biplots identified TNPSc 2138 and TNPSc 2163 as highly stable with superior mean performance. In the case of culm strength, mutants TNPSc 2138, TNPSc 2163, and TNPSc 2132 exhibited high stability and strong lodging tolerance across environments. For single plant yield, AMMI, and GGE analyses consistently confirmed TNPSc 2138 and TNPSc 2163 as the most stable and high-yielding genotypes, combining superior mean performance with minimal interaction effects. The MGIDI index, integrating multiple traits at 15
Quality control of mRNAs ensures that only properly processed transcripts are exported from the nucleus. Myosin-like protein 1 (Mlp1), plays a central role in this process by interacting with RNA-binding proteins (RBPs), including Nab2. While previous studies identified Phe73 in Nab2 as critical for Mlp1 binding, the molecular mechanism remains unclear. Here, we employed a computational approach to develop a mechanistic model of Mlp1-Nab2 interaction. Our results suggest that Phe73 does not act through direct contacts with Mlp1, but instead stabilizes intramolecular interactions between Nab2 helices that promote a compact conformation. F73A disrupted this helix-helix stabilization and weakened binding, whereas F73W enhanced the interaction. Our findings support a binding mechanism in which the structural flexibility of Mlp1's disordered domain enables adaptive recognition of Nab2. This mechanism may represent a general strategy by which the nuclear basket inspects mRNPs, highlighting the importance of flexible protein-protein recognition in mRNA quality control.
The nucleus is a structurally diverse and dynamic organelle that anchors chromatin and orchestrates a large number of essential processes, including transcription, replication, ribosome biogenesis, and nucleocytoplasmic transport. Understanding how nuclear macromolecular assemblies are organized and coordinate these processes requires high-resolution imaging methods, capable of achieving sub-molecular resolution while preserving native cellular structures. Cryo-electron tomography (cryo-ET) now provides unprecedented three-dimensional views of nuclear architecture in situ, up to sub-nanometer resolution. In this review, we discuss how cryo-ET has reshaped our understanding of nuclear biology including chromatin organization, nuclear pore complex (NPC) architecture and dynamics, and chromatin - lamina interactions. We highlight how these insights have resolved long-standing debates in biology, linked nuclear structure to function, and set the stage for future developments that will bridge molecular and cellular scales.
Nuclear positioning drives developmental processes from fertilization to neurogenesis. The linker of nucleoskeleton and cytoskeleton (LINC) complex connects nuclei to cytoskeletal force generators that power nuclear migration. Mutations in LINC complex components cause muscular dystrophies and neurodegenerative disorders, yet mechanisms controlling nuclear movement remain poorly understood. We summarize advances from three C. elegans developmental models in different mechanical environments: pronuclear migration across the vast zygotic cytoplasm, hyp7 hypodermal precursor nuclear migration where nuclei span nearly the width of the cell, and P-cell nuclear migration through narrow constrictions. These systems reveal multiple regulatory strategies for nuclear movement. Tissue-specific expression of distinct SUN-KASH combinations determines which cytoskeletal elements engage nuclei. Alternative splicing generates KASH isoforms with opposing motor preferences, and P-cell nuclear migration through constrictions requires four parallel pathways. These findings establish conserved mechanistic principles of nuclear migration, with implications for development, immune cell function, and cancer metastasis.
The state of Haryana in India is known for its archaeological sites related to the Indus Valley Civilisation and is a region of high ethnic and linguistic diversity. However, insufficient forensic DNA data is available from this region. The present study addresses this gap by genotyping 253 individuals using the Microreader™ 28 A ID system. The results show that all 24 loci were highly polymorphic, with a combined discrimination power and exclusion power of 1. Most loci demonstrated high informativeness, confirming their forensic efficacy in the studied population. Population genetic analyses revealed significant structure—the general Haryana population occupied an intermediate genetic position, while subgroup analyses showed distinct ancestries, reflecting complex social substructure of the region. Our findings highlight the necessity of population-specific validation of STR marker efficacy, especially for endogamous Indian populations. In summary, this study affirms that the Microreader™ 28 A ID system is a powerful and reliable tool for forensic DNA profiling and paternity testing in this Indian population. Furthermore, this comprehensive dataset provides valuable insights into the genetic history and demographic dynamics of North India. This article aligns with SDG 15 (Life on Land) of the UN Agenda for Sustainable Development.
Defining the role mechanical forces play in determining cell identity and function is imperative to interpreting cellular and physiological phenomena, as well as inspiring the development of novel therapeutics. As the field of mechanotransduction has grown in size and appreciation, there have been great strides in defining the molecular mechanisms by which cells respond to their mechanical environment. This includes characterization of the interface between the cell’s surface and the extracellular matrix (ECM) via integrin-based adhesions, as well as a deeper understanding of the nucleus as a force sensor capable of driving changes to gene expression. However, disentangling mechanosensitive cellular pathways has proven challenging, particularly defining if and how characterized cellular mechanosensors work in parallel or in unison. In this review, we will highlight the interplay between integrin-ECM adhesions and the nucleus, summarizing what is currently understood about how mechanical information is relayed and integrated across these two mechanoresponsive entities.
Oral squamous cell carcinoma (OSCC) is the most common aggressive malignancy of the head and neck squamous cell carcinoma (HNSCC) subtype. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by target degradation or inhibition of translation. miR-21-5p is a multifaceted miRNA found to be overexpressed and acts as a potent oncogene, regulating various cellular pathophysiology, such as cell proliferation, invasion, migration, and apoptosis, in many cancers, including OSCC. Despite its established involvement in OSCC progression, the upstream regulators of miR-21-5p and its downstream targets are still not completely elucidated. Transforming growth factor-beta (TGF-β) is a cytokine that shows a paradoxical role in diverse diseases, including OSCC. TGF-β exerts oncogenic effects in OSCC, shown by the induction of mesenchymal markers, which may account for the metastatic potential of OSCC. Through small RNA sequencing of SCC-25 cells treated with TGF-β, we identified numerous miRNAs that were induced in OSCC. Further, this study confirms the positive correlation between the TGF-β pathway and miR-21-5p induction, in which miR-21-5p is transcriptionally induced by the SMAD-mediated TGF-β signaling pathway. Mechanistically, TGF-β-induced miR-21-5p exerts its oncogenic effects in OSCC by post-transcriptionally suppressing its target, the transcription factor KLF5 (Kruppel-like factor 5). Loss-of-function studies on KLF5 confirmed its tumor suppressive role in SCC-25 and SCC-9 OSCC cells. Taken together, our study reports for the first time the existence of a TGF-β/miR-21-5p/KLF5 regulatory axis in OSCC, which could potentially be of therapeutic value. This article aligns with SDG 3 (Good Health and Well-Being) of the UN Agenda for Sustainable Development.
The primary experimental objective of the present investigation is to study the targeted genome editing of the myostatin (MSTN) gene using ribonucleoprotein (RNP) complexes composed of Cas9 protein and single guide RNA (sgRNA). Muscle tissue from PB-1 line of chicken was used to clone the myostatin gene and sequenced using oxford nanopore technology to identify genetic variants. The sgRNAs were designed for further validation by CRISPR-Cas9 Ribonucleoprotein Complex. The Cas9 protein was incubated with sgRNA to form the RNP complex. The PCR amplification of myostatin gene produced a distinct band of 1128 bp. Analysis of the sequencing results confirmed the total size of the recombinant plasmid to be 4128 bp and the insert length of 1128 bp encoding a protein of 375 amino acids. Two single nucleotide polymorphisms (SNPs) were identified—a cytosine-to-thymine substitution at position 672 bp and a thymine-to-guanine substitution at position 699 bp of the coding region of the gene. Both the SNPs were synonymous mutations that did not alter the amino acid sequence. Incubation of PCR products with the assembled RNP complex resulted in three distinct DNA bands of 1128 bp, 764 bp, and 364 bp for sgRNA1 and 1128 bp, 835 bp and 293 bp for sgRNA2. In control samples, a band at approximately 1128 bp was observed. This pattern indicates specific cleavage by the RNP complex and our assay successfully identified two functional sgRNAs for MSTN, providing validated tools for subsequent genome editing efforts in the Indian PB-1 chicken line. This article aligns with SDG 2 (Zero Hunger) of the UN Agenda for Sustainable Development.
Sheath blight (ShB) caused by the necrotrophic fungus Rhizoctonia solani, is a major disease of rice, with no completely resistant genotype identified to date. In the present study, a major QTL, qShB-1.1, covering 0.77 megabase (Mb) interval at the telomeric end of the long arm in chromosome 1, was consistently identified from a biparental mapping population of 384 recombinant inbred lines (RILs) derived from moderately resistant genotype CR 1014 and susceptible genotype Swarna-Sub1. Validation in contrasting RILs and backcross-derived inbred lines (BILs) through field-based phenotyping, glass house screenings, and bioassay confirmed a strong association between the flanking markers and ShB response. Colocalization of qShB-1.1 identified the corresponding chromosomal location as a genomic hotspot for ShB resistance QTLs. Within qShB-1.1, 122 genes were annotated, out of which 17 were shortlisted based on their tissue-specific expressions reported in databases and literature. Six of these genes were directly identified from the differential proteomics dataset of the parents generated at different time intervals after inoculation. Three other genes, LOC_Os01g65800, LOC_Os01g65650, and LOC_Os01g65450, exhibited significantly higher expression as determined by quantitative real-time PCR (qRT-PCR) in all resistant genotypes. Cis-regulatory elements, including methyl jasmonate (MeJA) and other stress-responsive motifs, were identified in these genes, suggesting their putative role in ShB defense responses. Additionally, 98 co-expressed genes, for these three genes, were predicted and further verified in the differential proteomic dataset. The stable QTL qShB-1.1 thus represents a valuable genomic resource that could be deployed in marker-assisted breeding and gene pyramiding to mitigate one of the most critical diseases of rice. This article aligns with SDG 2 (Zero Hunger) of the UN Agenda for Sustainable Development.
This study characterized the phytochemical composition and mineral elements of Bhut jolokia (Ghost chili, Capsicum chinense), one of the most pungent chili species. In vivo pilot genotoxic assays indicated that capsaicin (30 mg/kg bw) and Bhut jolokia fruit extract (100 mg/kg bw) significantly attenuate Benzo(a)pyrene [B(a)P]-induced genotoxicity. Morphological, histopathology, immunohistochemistry, and western immunoblot studies together demonstrated that, capsaicin and Bhut jolokia extract administered Swiss albino mice showed reduction in the B(a)P induced tumour incidence, multiplicity, number and size of the tumour nodule in the lung tissues by down-regulating the expressions of cancer marker proteins like Nf-kB and PCNA. As such, the present in vivo study demonstrated that daily intake of highly pungent Bhut jolokia in a normal diet is rather beneficial for reducing environmental carcinogenicity. This article aligns with SDG 3 (Good Health and Well-Being) of the UN Agenda for Sustainable Development.
Olivetol (5-pentylresorcinol) is a naturally occurring alkylresorcinol whose cellular mechanism remains poorly understood. Here, we show that olivetol induces a non-genotoxic nucleolar DNA damage response (n-DDR) in human cells. Although moderately cytotoxic, olivetol did not cause detectable genomic DNA double-strand breaks. Instead, it triggered γH2AX accumulation at ribosomal DNA (rDNA), recruitment of TOPBP1 to Treacle, nucleolar disorganization, and repression of ribosomal RNA synthesis. Mechanistically, olivetol closely phenocopied hypotonic stress, inducing a rapid and reversible n-DDR associated with antisense RNA polymerase II transcription within the rRNA coding region and accumulation of R-loops, consistent with transcriptional interference between RNA polymerases I and II. Both olivetol and hypotonic stress also produced shared membrane-associated phenotypes, including reduced membrane lipid order, calcium redistribution, and plasma membrane blebbing. Importantly, this non-genotoxic nucleolar response depended on cholesterol-sensitive plasma membrane organization.
Imaging of recruitment of XRCC1 and PCNA to a predetermined number of DNA single-strand breaks (SSB) demonstrates that (i) short-patch base excision repair is active throughout the whole cell cycle and repairs SSBs in over 60% of nonreplicating cells, while long-patch BER is active in approximately 30% of nonreplicating cells, becomes inactive in the early S phase and shows activity again in the mid and late S phase (in 8 and 16% of cells, respectively), (ii) cells retain the capacity to respond to damage if the total number of SSBs induced within seconds does not exceed approximately 110, more breaks evoke no XRCC1 recruitment; (iii) within less than a second, a cell commits a part of the currently available pool of XRCC1 molecules to accumulation at the damage site. We hypothesize that a limit on the number of single-strand breaks that elicit the BER response can arise from limited poly-ADP-ribosylation.
Mucilage, a complex hydrated polysaccharide matrix is extruded upon seed hydration (called myxospermy) in many angiosperms. It facilitates critical ecological and physiological functions like germination, enhancement of seed dispersal, maintaining hydration, etc. One of the significant commercial sources of mucilage is Plantago ovata that has been valued for its tremendous medicinal and industrial applications. Latterly, efforts have been made to elucidate the mucilage pathway in Arabidopsis thaliana, Plantago ovata and other myxospermous plants. These studies have highlighted that compositional variation in the mucilage derived from different plants leads to variable gel-forming and hydrocolloid properties. Unlike, Arabidopsis mucilage which is predominantly composed of pectin, mucilage in Plantago is made up of hemicellulose while in other plants mucilage has both pectin and hemicellulose. In Arabidopsis thaliana, the differentiation of mucilage secretory cells in the seed coat is well documented unraveling the intricate process of cell expansion, pectin biosynthesis, secretion, in muro pectin modification and secondary cell wall synthesis along with the involvement of several regulatory genes and enzymes. Although, substantial amount of information has become available for this model plant, yet mucilage biosynthetic pathway still awaits to be elucidated fully, along with the identification of additional genes and the related processes. P. ovata produces more and slightly larger seeds with 20-30
