Diverse Regulatory Mechanisms Research Articles (Page 1)

The 70-kDa heat shock protein (Hsp70) chaperone is essential to maintain cellular protein homeostasis, facilitating the folding, assembly, membrane translocation and quality control of proteins. Hsp70s achieve their functions through 'selective promiscuity', interacting with a wide range of substrate proteins while minimizing undesired interactions. J-domain proteins (JDPs) and nucleotide exchange factors (NEFs) are key to substrate recognition, remodelling and release from chaperone complexes. JDPs either target Hsp70s to specific subcellular sites where substrates reside (recruiters) or bind substrates directly by using highly specific (specialists) or multiple, versatile (generalists) binding sites. Through diverse substrate-binding modes and regulatory mechanisms, the 50 human JDPs confer remarkable client specificity to Hsp70s, a function that is comparable to that achieved by close to 600 E3 ubiquitin ligases in targeting proteins for degradation. Moreover, JDPs, together with NEFs, dictate the fate of Hsp70 clients by directing them to distinct protein quality control pathways, resulting in their folding or degradation. These recent mechanistic insights into Hsp70 regulation not only highlight the versatility and complexity of the Hsp70 network but also offer new avenues for more specific interventions in ageing-related and other protein folding diseases.

TET enzymes: Involvement in cancer development and therapeutical perspectives.

A shared basis for nutrient limitation response in cyanobacteria.

Plant seeds have evolved diverse dormancy types and regulatory mechanisms to adapt to environmental conditions and seasonal changes. As a commonly used rootstock for cultivated pears, Pyrus betulaefolia faces challenges in seedling production and large-scale cultivation due to limited understanding of seed dormancy mechanisms. In this study, we report that Pyrus betulaefolia seeds exhibit non-deep physiological dormancy, with seed coats playing a pivotal regulatory role. Exogenous abscisic acid (ABA) treatment, fluridone application and seed coat bedding assay demonstrated that dormant seed coats actively synthesized ABA to inhibit embryo germination during imbibition. ABA in imbibed dormant seed coats stimulated ABA biosynthesis in embryos, leading to increased expression of genes involved in ABA biosynthesis (PbeNCED-3) and ABA-responsive (PbeABI3-1, PbeABI5-1, and PbeABI5-5). Importantly, PbeABI5-5 directly binds to the promoters of GIBBERELLIN 2-OXIDASE 3/4 (PbeGA2ox-3/4) to activate their transcription. We establish that in dormant Pyrus betulaefolia seeds, the seed coat controls embryo dormancy release through coordinated regulation of PbeABI5-GA2ox module, thereby maintaining the critical balance between ABA and GA.

Diverse epigenetic regulatory mechanisms ensure and regulate cellular diversity. Among others, the histone 3 lysine 9 me3 (H3K9me3) post translational modification participates in silencing lineage-inappropriate genes. H3K9me3 restricts access of transcription factors and other regulatory proteins to cell-fate controlled genes. In mice, olfactory sensory neurons (OSN) express one olfactory receptor (OR) gene out of 2,600 possibilities. This monoallelic and stochastic OR choice happens as OSNs differentiate and undergo dramatic changes in nuclear architecture. OR genes from different chromosomes converge into specialized nuclear bodies and chromatin compartments as H3K9me3 and chromatin binding proteins including heterochromatin protein 1 (HP1) are incorporated. In this work, we have uncovered an unexpected role for HP1β in OR choice and neuronal identity that cannot be rescued by HP1α in vivo. With the use of a conditional knock-in mouse model that replaces HP1β for HP1α, we observe changes in H3K9me3 levels, DNA accessibility, and Hi-C contacts over OR gene clusters. These changes alter the expression patterns that partition the mouse olfactory epithelium into five OR expression zones, which results in a reduced OR repertoire leading to a loss of olfactory sensory neuron diversity. We propose that HP1β modulates the competition of OR-promoters for enhancers to promote receptor diversity, by establishing repression gradients in a zonal fashion.

Caenorhabditis elegans, a free-living nematode model, secretes neuropeptides, but the ecological roles of its peptide exudates in regulating rhizosphere microbial activity remain largely unexplored. We identified six short peptides (P1, P9, P19, P20, P25, and P26) from C. elegans exudates that significantly enhanced indole-3-acetic acid (IAA) production by the plant growth-promoting bacterium Arthrobacter pascens ZZ21. These peptides were heat-labile and proteinase K-sensitive but unaffected by DNase I or RNase A, confirming their proteinaceous (peptide) nature rather than nucleic acid origin. The retention of bioactivity in n-butanol extracts further supported their hydrophilic, peptide-like properties. LC-MS/MS identified 30 linear peptides, including the six bioactive ones, which exhibited distinct dose-dependent effects, suggesting diverse regulatory mechanisms. Despite their relatively low abundance, these peptides strongly promoted IAA production in the bacterial culture system across multiple concentrations. These findings reveal an unrecognized mechanism whereby free-living nematodes regulate rhizobacterial metabolism via secreted peptides, offering new insights into nematode-mediated chemical signaling. Therefore, this study advances understanding of plant-microbe-nematode interactions and highlights strategies for manipulating rhizosphere microbiota in sustainable agriculture.

Mitochondrial transcription factor a as a guardian of mitochondrial integrity and emerging therapeutic target in human diseases: A review.

Endoplasmic Reticulum (ER) stress disrupts protein homeostasis and impacts protein dynamics, driving cellular responses critical for survival, development and disease. However, no current proteome-wide technology enables simultaneous identification of proteins undergoing altered synthesis and clearance and distinguish their relative contribution during ER stress. To fill this gap, we developed Integral Synthesis and clearance analysis via DIA (ISDia), a robust mass spectrometry-based platform that integrates pulsed-SILAC labeling with data-independent acquisition (DIA) to quantify heavy and light peptide changes and determine the drivers of protein dynamics with high proteome coverage under non-steady-state conditions. Using ISDia, we uncover diverse regulatory mechanisms by which protein synthesis and clearance are modulated to control protein abundances during ER stress, revealing PERK dependent and independent regulatory mechanisms across subcellular compartments, complexes and isoforms. These findings highlight the potential of ISDia as a powerful and widely applicable platform for elucidating protein dynamic regulatory mechanisms.

NAC (NAM, ATAF1/2, CUC1/2) is a plant-specific transcription factor (TF) family that plays important roles in various physiological and biochemical processes of plants. However, the NAC gene family in Lagerstroemia indica and its role in anthocyanin metabolism are still unexplored. In our study, a total of 167 NACs were identified in the L. indica genome via genome-wide analysis and bioinformatics techniques. Amino acid sequence analysis showed that all 167 NAC proteins contained a conserved NAM domain. This domain primarily comprised random coils, extended strands, and alpha helices. Most NACs were found on the nucleus and dispersed over 23 of the 24 plant chromosomes. Based on phylogenetic analysis, the NACs can be categorized into ten subgroups. Furthermore, the promoter homeotropic elements predicted the cis-acting elements in the promoters of these genes related to hormones, development, environmental stress response, and other related responses, demonstrating the diverse regulatory mechanisms underlying gene functions. In addition, a co-expression network was established through RNA sequencing. This network helped identify seven key LiNACs, genes related to anthocyanin expression (CHS) and transcription factors (MYB and bHLH). To identify potential anthocyanin regulatory factors present in L. indica petals, protein interaction prediction was performed, which revealed that LiNACs might participate in anthocyanin regulation by interacting with other proteins, such as MYB, ABF, ABI, bZIP, MYC, etc. Our results provided novel insights and could help in the functional identification of LiNACs in L. indica and the regulation of anthocyanin synthesis.

Objective:The objective of this study is to explore the role and regulatory mechanisms of disulfidoptosis in spinal cord injury (SCI) and to develop a diagnostic model based on this cell death mechanism.Methods:The peripheral blood RNA-seq data from SCI patients sourced from dataset GSE151371 was utilized in the study. Various analytical techniques, including differential gene expression analysis, immune infiltration profiling, consistency clustering, and pathway enrichment analysis, were employed to investigate the impact of disulfidoptosis. Machine learning models were also developed to aid in the diagnosis of SCI based on gene expression profiles related to disulfidoptosis.Results:Gene expression analysis revealed significant upregulation of genes such as GYS1, PDLIM1, NDUFA11, and MYL6, and downregulation of NUBPL, LRPPRC, and CD2AP in SCI patients, with statistical significance (P < .05). Immune infiltration profiling showed a decrease in CD4+ and CD8+ T cells, contrasted by an increase in gamma delta T cells (P < .05), indicating an altered immune landscape. Furthermore, 2 distinct subgroups were identified through consistency clustering, highlighting significant differences in disulfidoptosis-related gene expression. Pathway enrichment analysis revealed different pathways between clusters, suggesting diverse regulatory mechanisms within SCI subtypes. The diagnostic model evaluation using random forest achieved the highest accuracy with an area under the curve (AUC) of 0.955, demonstrating its potential utility in clinical settings for SCI diagnosis.Conclusion:Disulfidoptosis plays a significant role in the pathophysiology of SCI. This study offers novel insights into its molecular mechanisms and presents a potential foundation for diagnostic modeling.Level of Evidence:Level IV, Diagnostic Study.

SUMMARYThe leaf angle (LA) is a critical component of plant architecture that directly influences photosynthetic efficiency and grain yield. In the present study, we found that ETHYLENE RESPONSE FACTOR 101 (OsERF101), an APETALA2/ethylene response factor, plays a role in LA formation. A null mutation in OsERF101 resulted in reduced LA, whereas transgenic plants overexpressing OsERF101 (OsERF101‐OEs) exhibited increased LA. OsERF101 increased the development of the adaxial lamina joint (LJ). Transactivation assays and reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) analysis indicated that OsERF101 activated BRASSINOSTEROID UPREGULATED 1 (OsBU1) transcription by directly binding to its promoter. However, OsERF101 expression was suppressed by exogenous brassinosteroid (BR) treatment and elevated endogenous brassinolide (BL) levels during LJ development. Additionally, OsERF101 downregulated the expression of BR biosynthesis genes, including Brassinosteroid‐deficient dwarf2 (OsBRD2) and CYP90B2/OsDWARF4, leading to reduced levels of endogenous BL, the most active BR, in OsERF101‐OEs. These findings suggested that OsERF101 mediates a negative feedback loop that balances endogenous BR levels and signaling. Collectively, rice plants have evolved diverse regulatory mechanisms involving OsERF101 to tune LA formation and optimize plant architecture finely.

Stomatal closure in response to water deficit is crucial for maintaining plant water balance. While the mechanisms driving daytime stomatal closure under drought are well studied, the mechanism driving progressive declines in nighttime transpiration (Enight) during drought remains less understood. To investigate whether either abscisic acid (ABA) or declining leaf water status drives progressive declines in Enight during drought in vascular plants, we conducted experiments using representative fern, gymnosperm, and angiosperm species, including a severe ABA-deficient mutant and tree species. These species span a spectrum of stomatal control by ABA, ranging from insensitive to endogenous ABA in the fern to reliance on ABA for stomatal closure in the herbaceous angiosperm. We found that reductions in Enight during drought are driven by hydropassive stomatal closure in ferns and gymnosperms, transitioning to ABA regulation in gymnosperms under severe stress, and are triggered by ABA in herbaceous angiosperms. In all species, the proportion of total transpiration occurring at night increased as stomata closed during the drought. The reduction of Enight during drought appears to be a convergent stomatal response across vascular land plants but is driven by diverse regulatory mechanisms linked to evolutionary history and ecological strategy.

Therapeutic role of caveolin family in stem cell fate and development for management of chronic degenerative diseases: A scientometric study to an in-depth review.

Small RNAs (sRNAs) are pivotal in regulating gene expression and are involved in a diverse array of biological processes. Among these, microRNAs (miRNAs) and phased small interfering RNAs (phasiRNAs) have been extensively investigated over the past decades. We conducted an in-depth analysis of deep sequencing data from the gymnosperm Ginkgo biloba, encompassing sRNA, transcriptome, and degradome libraries. Our analysis identified a total of 746 miRNAs and 654 phasiRNA precursor (PHAS) loci, with 526 (80%) of the PHAS loci predicted to be triggered by 515 miRNAs (69%). Several miRNA-PHAS modules, particularly the miR159/miR319-PHAS module, were found to potentially regulate reproductive development by targeting GAMYB genes and triggering phasiRNA biogenesis. The miR390-PHAS module appears to be involved in flavonoid biosynthesis by targeting key enzyme genes such as chalcone synthase (CHS) and anthocyanin synthase (ANS). Through target gene identification and coexpression analysis, we uncovered two distinct models of complex regulatory networks: growth-related factors like ARF and GRF seem to be regulated exclusively by miRNAs (Model 1), while certain disease resistance-related genes are predicted to be regulated by both miRNAs and phasiRNAs (Model 2), indicating diverse regulatory mechanisms across different biological processes. Overall, our study provides a comprehensive annotation of miRNA and PHAS loci in G. biloba and elucidates a post-transcriptional regulatory network, offering novel insights into sRNA research in gymnosperms.

Extreme acidophiles from the Acidithiobacillia class thrive in highly acidic environments where they rely on diverse regulatory mechanisms for adaptation. These mechanisms include sigma factors, transcription factors (TFs), and transcription factor binding sites (TFBS), which control essential pathways. Comparative genomics and bioinformatics analyses identified sigma factors and TFs in Acidithiobacillia, showing similarities but key differences from reference neutrophiles. This study highlights sigma54-dependent one- and two-component systems that are crucial for survival in energy acquisition from sulfur compounds and hydrogen as well as nutrient assimilation. Furthermore, the data suggested evolutionary divergence in regulatory elements distinguishes S-oxidizing from Fe-S-oxidizing members of Acidithiobacillia. Conservation of gene clusters, synteny, and phylogenetic analyses supported the expected phenotypes in each species. Notable examples include HupR’s role in hydrogenase-2 oxidation in Fe-S-oxidizers, TspR/TspS regulation of the sulfur oxidation complex, and FleR/FleS control of flagellar motility in S-oxidizers. These regulatory mechanisms act as master controllers of bacterial activity, reflecting adaptation to distinct metabolic needs within Acidithiobacillia.

Decoding the transcriptional regulatory mechanisms of basic helix-loop-helix transcription factors for fine-tuning target genes in rice.

The significant rise in soil salinity has had detrimental effects on global agricultural production, negatively impacting overall plant health and leading to a decline in productivity. As a protective response, plants have developed diverse regulatory mechanisms to counteract these adverse conditions. The mechanisms help mitigate damage caused by both osmotic and ionic stress resulting from high salinity. Given the severe threat this poses to global food security and the well-being of the world's population, scientists have dedicated decades of research to understanding how to manage salt stress. Numerous mechanisms have been identified and studied to enhance plant salt tolerance and alleviate the damage caused by salt stress. This review examines recent advancements in molecular regulatory mechanisms underlying plant salt, including salt uptake and transport, salt sensing and signalling, hormonal regulation, epigenetic modifications, genetic adaptation, and posttranslational modifications. Although current knowledge has advanced our understanding, critical gaps and controversies remain, such as the stability of epigenetic memory, the trade-off between stress tolerance and growth, hormonal crosstalk, and novel genes with uncharacterised roles in salt tolerance. To resolve these questions, further research employing techniques like GWAS, transcriptomics, transgenic and genome-editing technologies, as well as studies on energy allocation and hormonal regulation, is essential. A deeper exploration of these complex, synergistic mechanisms will pave the way for enhancing plant resilience and ensuring adaptation to increasingly challenging environmental conditions.

Frequent dysregulation of multiple circular RNA isoforms with diverse regulatory mechanisms in cancer - Insights from circFNDC3B and beyond: Why unique circular RNA identifiers matter.

The sugar transporter proteins in plants: An elaborate and widespread regulation network-A review.

Heat shock proteins, HSP70, are vital for plant stress response mechanisms, particularly under abiotic stresses, such as salinity and drought. However, its role in Beta vulgaris is still unknown. We conducted a comprehensive genome-wide analysis of the BvHSP70 gene family in B. vulgaris roots to elucidate their diverse functions, regulatory mechanisms, and roles in abiotic stress adaptation. We identified 22 BvHSP70 genes, characterized by conserved motifs and cis elements associated with stress response in the gene promoters. miRNA interactions suggest regulatory roles, while gene duplication and syntenic analysis were utilized to reveal evolutionary trends with insights into gene expansion and conservation across species. These findings indicate the involvement of BvHSP70 genes in stress adaptation and broader biological processes. Key regulatory miRNAs were identified in two BvHSP70 genes. Expression analysis under salt stress indicated significant upregulation of BvHSP70-2 gene, BvHSP70-15 gene, and BvHSP70-17 gene after 1 day, whereas BvHSP70-18 showed notable upregulation after 7 days. Under drought stress, BvHSP70-4, BvHSP70-13, and BvHSP70-14 were significantly downregulated, whereas BvHSP70-17 and BvHSP70-20 were significantly upregulated. These findings demonstrate the critical function of the BvHSP70 family in B. vulgaris stress adaptation. Understanding the functional and regulatory mechanisms of BvHSP70 can facilitate the development of strategies to enhance stress tolerance in B. vulgaris and other crops, thereby contributing to agricultural sustainability and food security.