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Frontiers in Genetics 2024Small RNAs (sRNAs) are important non-coding RNA regulators that play key roles in the development and pathogenesis of plant pathogens, as well as in other biological...
Small RNAs (sRNAs) are important non-coding RNA regulators that play key roles in the development and pathogenesis of plant pathogens, as well as in other biological processes. However, whether these abundant and varying sRNAs are involved in development or infection remains enigmatic. In this study, sRNA sequencing of 4 asexual stages of (), namely, as mycelia (HY), sporangia (SP), zoospores (ZO), cysts (CY), and pepper infected with (IN), were performed, followed by sRNA analysis, microRNA (miRNA) identification, and miRNA target prediction. sRNAs were mainly distributed at 25-26 nt in HY, SP, and ZO but distributed at 18-34 nt in CY and IN. 92, 42, 176, 39, and 148 known miRNAs and 15, 19, 54, 13, and 1 novel miRNA were identified in HY, SP, ZO, CY, and IN, respectively. It was found that the expression profiles of known miRNAs vary greatly at different stages and could be divided into 4 categories. Novel miRNAs mostly belong to part I. Gene ontology (GO) analysis of known miRNA-targeting genes showed that they are involved in the catalytic activity pathway, binding function, and other biological processes. Kyoto Encyclopedia of Gene and Genome (KEGG) analysis of novel miRNA-targeting genes showed that they are involved in the lysine degradation pathway. The expression of candidate miRNAs was validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and miRNAs were downregulated in or mutants. To further explore the function of the detected miRNAs, the precursor of a novel miRNA, miR91, was knockout by CRISPR-Cas9, the mutants displayed decreased mycelial growth, sporangia production, and zoospore production. It was found that 503142 (Inositol polyphosphate 5-phosphatase and related proteins) can be predicted as a target of miR91, and the interaction between miR91 and 503142 was verified using the tobacco transient expression system. Overall, our results indicate that the diverse and differentially expressed sRNAs are involved in the development and pathogenesis of
PubMed: 38919951
DOI: 10.3389/fgene.2024.1296533 -
Frontiers in Genetics 2024Moyamoya disease (MMD) is a chronic cerebrovascular disease that can lead to ischemia and hemorrhagic stroke. The relationship between oxidative phosphorylation...
Moyamoya disease (MMD) is a chronic cerebrovascular disease that can lead to ischemia and hemorrhagic stroke. The relationship between oxidative phosphorylation (OXPHOS) and MMD pathogenesis remains unknown. The gene expression data of 60 participants were acquired from three Gene Expression Omnibus (GEO) datasets, including 36 and 24 in the MMD and control groups. Differentially expressed genes (DEGs) between MMD patients MMD and control groups were identified. Machine learning was used to select the key OXPHOS-related genes associated with MMD from the intersection of DEGs and OXPHOS-related gene sets. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), gene set enrichment analysis (GSEA), Immune infiltration and microenvironments analysis were used to analyze the function of key genes. Machine learning selected four key OXPHOS-related genes associated with MMD: , , and ( was upregulated and the other three were downregulated). Functional enrichment analysis showed that these genes were mainly enriched in the Notch signaling pathway, GAP junction, and RNA degradation, which are related to several biological processes, including angiogenesis, proliferation of vascular smooth muscle and endothelial cells, and cytoskeleton regulation. Immune analysis revealed immune infiltration and microenvironment in these MMD samples and their relationships with four key OXPHOS-related genes. APC co-inhibition ( = 0.032), HLA ( = 0.001), MHC I ( = 0.013), T cellco- inhibition ( = 0.032) and Type I IFN responses ( < 0.001) were significantly higher in the MMD groups than those in the control groups. The positively correlated with APC co-inhibition and T cell-co-inhibition. The negatively correlated with Type I IFN response. The negatively correlated with APC co-inhibition and Type I IFN response. The positively correlated with HLA, MHC I and Type I IFN responses. This study provides a comprehensive understanding of the role of OXPHOS in MMD and will contribute to the development of new treatment methods and exploration of MMD pathogenesis.
PubMed: 38919950
DOI: 10.3389/fgene.2024.1417329 -
Medical Review (2021) Jun 2024RNA-based therapeutics have emerged as a promising approach for the treatment of various diseases, including cancer, genetic disorders, and infectious diseases. However,... (Review)
Review
RNA-based therapeutics have emerged as a promising approach for the treatment of various diseases, including cancer, genetic disorders, and infectious diseases. However, the delivery of RNA molecules into target cells has been a major challenge due to their susceptibility to degradation and inefficient cellular uptake. To overcome these hurdles, DNA-based nano technology offers an unprecedented opportunity as a potential delivery platform for RNA therapeutics. Due to its excellent characteristics such as programmability and biocompatibility, these DNA-based nanostructures, composed of DNA molecules assembled into precise and programmable structures, have garnered significant attention as ideal building materials for protecting and delivering RNA payloads to the desired cellular destinations. In this review, we highlight the current progress in the design and application of three DNA-based nanostructures: DNA origami, lipid-nanoparticle (LNP) technology related to frame guided assembly (FGA), and DNA hydrogel for the delivery of RNA molecules. Their biomedical applications are briefly discussed and the challenges and future perspectives in this field are also highlighted.
PubMed: 38919398
DOI: 10.1515/mr-2023-0069 -
Current Medicinal Chemistry Jun 2024Theranostics, a method that combines targeted therapy and diagnostic imaging, has emerged as a viable route for enhancing cancer treatment, and hybrid nanoparticles...
Theranostics, a method that combines targeted therapy and diagnostic imaging, has emerged as a viable route for enhancing cancer treatment, and hybrid nanoparticles (HNPs) are at the forefront of this field. Metallic, polymeric, lipid-based, and silica- based HNPs are studied for targeting and biocompatibility. Using HNPs, chemotherapeutic drugs, small interfering RNA, and therapeutic genes can be given precisely and controlled. This enhances therapeutic efficacy and reduces adverse effects. With fluorescence dyes, MRI contrast agents, and PET tracers, real-time therapy response monitoring is conceivable. A nano platform with therapeutic and diagnostic capabilities holds great promise for personalized medicine and precision oncology. The present study discusses HNPs' biocompatibility, stability, immunogenicity, and long-term biosafety, which are crucial to the clinical translation of cancer theranostics. Further, in this in- -depth investigation, we investigated the design, synthesis, and multifunctional activities of HNPs for use in cancer theranostics.
PubMed: 38918993
DOI: 10.2174/0109298673309011240606095639 -
Journal of Nanobiotechnology Jun 2024Premature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human...
BACKGROUND
Premature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exs, H-Exs) have exhibited protective effects on ovarian function with unclear mechanisms.
METHODS
A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify POI-associated circRNAs and miRNAs. The relationship between HucMSC-derived exosomal circBRCA1/miR-642a-5p/FOXO1 axis and POI was examined by RT-qPCR, Western blotting, reactive oxygen species (ROS) staining, senescence-associated β-gal (SA-β-gal) staining, JC-1 staining, TEM, oxygen consumption rate (OCR) measurements and ATP assay in vivo and in vitro. RT-qPCR detected the expression of circBRCA1 in GCs and serum of patients with normal ovarian reserve function (n = 50) and patients with POI (n = 50); then, the correlation of circBRCA1 with ovarian reserve function indexes was analyzed.
RESULTS
Herein, we found that circBRCA1 was decreased in the serum and ovarian granulosa cells (GCs) of patients with POI and was associated with decreased ovarian reserve. H-Exs improved the disorder of the estrous cycles and reproductive hormone levels, reduced the number of atretic follicles, and alleviated the apoptosis and senescence of GCs in rats with POI. Moreover, H-Exs mitigated mitochondrial damage and reversed the reduced circBRCA1 expression induced by oxidative stress in GCs. Mechanistically, FTO served as an eraser to increase the stability and expression of circBRCA1 by mediating the mA demethylation of circBRCA1, and exosomal circBRCA1 sponged miR-642a-5p to block its interaction with FOXO1. CircBRCA1 insufficiency aggravated mitochondrial dysfunction, mimicking FTO or FOXO1 depletion effects, which was counteracted by miR-642a-5p inhibition.
CONCLUSION
H-Exs secreted circBRCA1 regulated by mA modification, directly sponged miR-642a-5p to upregulate FOXO1, resisted oxidative stress injuries in GCs and protected ovarian function in rats with POI. Exosomal circBRCA1 supplementation may be a general prospect for the prevention and treatment of POI.
Topics: Female; Granulosa Cells; Oxidative Stress; MicroRNAs; Animals; Exosomes; Rats; RNA, Circular; Humans; Primary Ovarian Insufficiency; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Forkhead Box Protein O1; Rats, Sprague-Dawley; Mesenchymal Stem Cells; Adult
PubMed: 38918838
DOI: 10.1186/s12951-024-02583-5 -
ALKBH5 regulates chicken adipogenesis by mediating LCAT mRNA stability depending on mA modification.BMC Genomics Jun 2024Previous studies have demonstrated the role of N6-methyladenosine (mA) RNA methylation in various biological processes, our research is the first to elucidate its...
BACKGROUND
Previous studies have demonstrated the role of N6-methyladenosine (mA) RNA methylation in various biological processes, our research is the first to elucidate its specific impact on LCAT mRNA stability and adipogenesis in poultry.
RESULTS
The 6 100-day-old female chickens were categorized into high (n = 3) and low-fat chickens (n = 3) based on their abdominal fat ratios, and their abdominal fat tissues were processed for MeRIP-seq and RNA-seq. An integrated analysis of MeRIP-seq and RNA-seq omics data revealed 16 differentially expressed genes associated with to differential mA modifications. Among them, ELOVL fatty acid elongase 2 (ELOVL2), pyruvate dehydrogenase kinase 4 (PDK4), fatty acid binding protein 9 (PMP2), fatty acid binding protein 1 (FABP1), lysosomal associated membrane protein 3 (LAMP3), lecithin-cholesterol acyltransferase (LCAT) and solute carrier family 2 member 1 (SLC2A1) have ever been reported to be associated with adipogenesis. Interestingly, LCAT was down-regulated and expressed along with decreased levels of mRNA methylation methylation in the low-fat group. Mechanistically, the highly expressed ALKBH5 gene regulates LCAT RNA demethylation and affects LCAT mRNA stability. In addition, LCAT inhibits preadipocyte proliferation and promotes preadipocyte differentiation, and plays a key role in adipogenesis.
CONCLUSIONS
In conclusion, ALKBH5 mediates RNA stability of LCAT through demethylation and affects chicken adipogenesis. This study provides a theoretical basis for further understanding of RNA methylation regulation in chicken adipogenesis.
Topics: Animals; Adipogenesis; RNA Stability; Chickens; Phosphatidylcholine-Sterol O-Acyltransferase; AlkB Homolog 5, RNA Demethylase; Female; Adenosine; RNA, Messenger; Methylation
PubMed: 38918701
DOI: 10.1186/s12864-024-10537-2 -
Scientific Reports Jun 2024Autophagy is a highly conserved eukaryotic pathway and plays a crucial role in cell survival under stress conditions. Here, we applied a full-length transcriptome...
Autophagy is a highly conserved eukaryotic pathway and plays a crucial role in cell survival under stress conditions. Here, we applied a full-length transcriptome approach to study an Arabidopsis autophagy mutant (atg5-1) subjected to nitrogen-starvation, using Oxford Nanopore Technologies. A total of 39,033 transcripts were identified, including 11,356 new transcripts. In addition, alternative splicing (AS) events and lncRNAs were also detected between Col-0 (WT) and atg5-1. Differentially expressed transcript enrichment showed that autophagy upregulates the expression of many stress-responsive genes and inhibits the transcription of photosynthesis-associated genes. The qRT-PCR results showed that the expression patterns of photosynthesis-related genes in the atg5-1 differed under the conditions of nitrogen starvation and carbon starvation. Under nitrogen starvation treatment, many genes related to photosynthesis also exhibited AS. Chlorophyll fluorescence images revealed that the Fv/Fm and ΦPSII of old atg5-1 leaves were significantly reduced after nitrogen starvation treatment, but the Y(NPQ) indices were significantly increased compared to those of the WT plants. The results of qRT-PCR suggest that autophagy appears to be involved in the degradation of genes related to photodamage repair in PSII. Taken together, the full-length transcriptiome sequencing provide new insights into how new transcripts, lncRNAs and alternative splicing (AS) are involved in plant autophagy through full-length transcriptome sequencing and suggest a new potential link between autophagy and photosynthesis.
Topics: Arabidopsis; Autophagy; Photosynthesis; Gene Expression Regulation, Plant; Transcriptome; Nitrogen; Alternative Splicing; RNA, Long Noncoding; Gene Expression Profiling; Arabidopsis Proteins; Autophagy-Related Protein 5
PubMed: 38918488
DOI: 10.1038/s41598-024-65555-7 -
Biomedicine & Pharmacotherapy =... Jun 2024Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is a serious disease for which a better understanding of prognostic factors and new therapeutic targets is needed....
Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is a serious disease for which a better understanding of prognostic factors and new therapeutic targets is needed. Circular RNAs (circRNAs) are promising markers due to their stability and differential expression patterns in various diseases. However, their role in pediatric B-ALL patients, particularly in risk stratification and relapse prediction, remains poorly understood. In this study, we comprehensively examined the circRNA landscape in pediatric B-ALL patients, focusing on both high-risk and standard-risk patients. Using advanced sequencing techniques and sophisticated bioinformatics tools, we identified thousands of circRNAs, including a novel circRNA derived from the WASHC2A gene, termed circWASHC2A. CircWASHC2A showed differential expression between high-risk and standard-risk patients and exhibited potential for predicting relapse in high-risk patients. Functional experiments highlighted a role for circWASHC2A in regulating cell cycle progression and mitochondrial respiratory activity in leukaemic cells. Transcriptomic analysis further supported these findings, suggesting the involvement of circWASHC2A in signalling pathways relevant to leukaemia pathogenesis. This study provides in-depth insights into the circRNA landscape of pediatric B-ALL patients and identifies circWASHC2A as a potential biomarker for risk stratification and relapse prediction, with significant implications for tailoring diagnostic and therapeutic strategies in this patient population.
PubMed: 38917755
DOI: 10.1016/j.biopha.2024.116903 -
Ecotoxicology and Environmental Safety Jun 2024Brassinosteroids (BRs) can regulate various processes in plant development and defense against environmental stress. In this study, the contribution of BRs in the...
Brassinosteroids (BRs) can regulate various processes in plant development and defense against environmental stress. In this study, the contribution of BRs in the degradation of isoproturon (IPU) in rice has been established. IPU has a significant effect on rice growth, chlorophyll content, and membrane permeability. When treated with 1.0 μmol/L 24-epibrassinolide (EBR), a BR analogue, the associated symptoms of rice poisoning were alleviated as the IPU levels in the rice and growth media were decreased. In the presence of EBR, the activities of several IPU-related detoxification enzymes were enhanced to cope with the stress due to IPU. An RNA-sequencing (RNA-Seq) has been performed to determine the variation of transcriptomes and metabolic mechanisms in rice treated with EBR, IPU, or IPU+EBR. Some of the differentially expressed genes (DEGs) were Phase I-III reaction components of plants, such as cytochrome P450 (CYP450), glutathione S-transferase (GST), glycosyltransferases (GTs), and the ATP-binding cassette transporter (ABC transporter). The expression of some signal transduction genes was significantly up-regulated. The relative content of low-toxicity IPU metabolites increased due to the presence of EBR as determined by UPLC/Q-TOF-MS/MS. The IPU metabolic pathways include enzyme-catalyzed demethylation, hydroxylation, hydrolysis, glycosylation, and amino acid conjugation processes. The results suggest that EBR plays a key role in the degradation and detoxification of IPU. This study has provided evidence that BRs regulate the metabolism and detoxification of IPU in rice, and offers a new approach to ensuring cleaner crops by eliminating pesticide residues in the environment.
PubMed: 38917591
DOI: 10.1016/j.ecoenv.2024.116575 -
Journal of Microbiology (Seoul, Korea) Jun 2024Aconitase-2 (Aco2) is present in the mitochondria, cytosol, and nucleus of fission yeast. To explore its function beyond the well-known role in the mitochondrial...
Aconitase-2 (Aco2) is present in the mitochondria, cytosol, and nucleus of fission yeast. To explore its function beyond the well-known role in the mitochondrial tricarboxylic acid (TCA) cycle, we conducted genome-wide profiling using the aco2ΔNLS mutant, which lacks a nuclear localization signal (NLS). The RNA sequencing (RNA-seq) data showed a general downregulation of electron transport chain (ETC) genes in the aco2ΔNLS mutant, except for those in the complex II, leading to a growth defect in respiratory-prone media. Complementation analysis with non-catalytic Aco2 [aco2ΔNLS + aco2(3CS)], where three cysteines were substituted with serine, restored normal growth and typical ETC gene expression. This suggests that Aco2's catalytic activity is not essential for its role in ETC gene regulation. Our mRNA decay assay indicated that the decrease in ETC gene expression was due to transcriptional regulation rather than changes in mRNA stability. Additionally, we investigated the Php complex's role in ETC gene regulation and found that ETC genes, except those within complex II, were downregulated in php3Δ and php5Δ strains, similar to the aco2ΔNLS mutant. These findings highlight a novel role for nuclear aconitase in ETC gene regulation and suggest a potential connection between the Php complex and Aco2.
PubMed: 38916790
DOI: 10.1007/s12275-024-00147-8