Post-transcriptional Gene Regulation Research Articles

Elucidating role of long non-coding RNAs of Tamarindus indica Linn. in post-transcriptional gene regulation

Tamarindus indica Linn., commonly known as tamarind, is a rich source of carbohydrates, proteins, lipids, fatty acids, vitamins, minerals and bioactive compounds. It is well established that long non-coding RNAs (lncRNAs) plays an important role in transcriptional, post-transcriptional and epigenetic regulation. Despite the availability of tamarind genome information, a handful of studies have been done on its non-coding genome, especially lncRNAs. In this study, we have computationally predicted lncRNAs from the coding DNA sequences of T. indica and analysed the sequences. We experimentally validated seven randomly chosen lncRNAs by performing quantitative Real Time Polymerase Chain Reaction (qRT-PCR). 320 lncRNAs have been predicted and sequence analysis of these predicted, lncRNAs reveals the presence of different motifs and tandem repeats. Along with the experimental validation of 7 randomly chosen lncRNAs, functional analysis of the predicted lncRNAs and their targets elucidated their roles in various biological pathways. We believe prediction and validation of the lncRNAs along with their interaction with mRNAs will enhance our knowledge about the non-coding genome of tamarind and their involvement in post transcriptional gene regulation, medicinal properties, metabolic engineering, stress tolerance and genome editing.

PmiRScan: a LightGBM based method for prediction of animal pre-miRNAs.

MicroRNAs (miRNA) are categorized as short endogenous non-coding RNAs, which have a significant role in post-transcriptional gene regulation. Identifying new animal precursor miRNA (pre-miRNA) and miRNA is crucial to understand the role of miRNAs in various biological processes including the development of diseases. The present study focuses on the development of a Light Gradient Boost (LGB) based method for the classification of animal pre-miRNAs using various sequence and secondary structural features. In various pre-miRNA families, distinct k-mer repeat signatures with a length of three nucleotides have been identified. Out of nine different classifiers that have been trained and tested in the present study, LGB has an overall better performance with an AUROC of 0.959. In comparison with the existing methods, our method 'pmiRScan' has an overall better performance with accuracy of 0.93, sensitivity of 0.86, specificity of 0.95 and F-score of 0.82. Moreover, pmiRScan effectively classifies pre-miRNAs from four distinct taxonomic groups: mammals, nematodes, molluscs and arthropods. We have used our classifier to predict genome-wide pre-miRNAs in human. We find a total of 313 pre-miRNA candidates using pmiRScan. A total of 180 potential mature miRNAs belonging to 60 distinct miRNA families are extracted from predicted pre-miRNAs; of which 128 were novel and are note reported in miRBase. These discoveries may enhance our current understanding of miRNAs and their targets in human. pmiRScan is freely available at http://www.csb.iitkgp.ac.in/applications/pmiRScan/index.php .

Small RNA CjNC110 regulates the activated methyl cycle to enable optimal chicken colonization by Campylobacter jejuni.

Post-transcriptional gene regulation by non-coding small RNAs (sRNAs) is critical for colonization and survival of enteric pathogens, including the zoonotic pathogen Campylobacter jejuni. In this study, we utilized C. jejuni IA3902 (a representative isolate of the sheep abortion clone) and C. jejuni W7 (a highly motile variant of NCTC 11168, a human gastroenteritis strain) to further investigate regulation by sRNA CjNC110. Both motility and autoagglutination ability were confirmed to be phenotypes of conserved regulation by CjNC110. However, we demonstrated that W7∆CjNC110 does not change chicken colonization levels compared to W7 wild type, directly contrasting IA3902∆CjNC110, which had decreased colonization ability. Subsequently, we determined strain-specific phenotype variation between W7∆CjNC110 and IA3902∆CjNC110 when examining intracellular L-methionine (L-met) levels controlled by the activated methyl cycle (AMC). We hypothesized that the presence of a secondary system for L-met production conferred by MetAB in W7 but not IA3902 might explain the difference in both chicken colonization and L-met availability. Insertion of metAB within IA3902∆CjNC110 (naturally absent) restored intracellular L-met levels in IA3902∆CjNC110::metAB and overcame the colonization defect that resulted from mutagenesis of CjNC110 in IA3902. Deletion of metAB in W7∆CjNC110 (naturally present) led to a decrease in L-met in W7∆CjNC110∆metAB and a colonization defect which was otherwise masked in W7∆CjNC110. Our results indicate that regulation of the AMC leading to altered L-met availability is a conserved regulatory function of CjNC110 in C. jejuni and confirm that L-met generation via the AMC as activated by CjNC110 is critical for optimal host colonization.IMPORTANCEDuring this study, the regulatory action and conservation of function of CjNC110 between two different zoonotically important Campylobacter jejuni strains were examined. Critically, this work for the first time reveals regulation of L-methionine (L-met) production within the activated methyl cycle (AMC) by small RNA (sRNA) CjNC110 as a key factor driving C. jejuni optimal chicken colonization. As a growing body of evidence suggests that maintenance of L-met homeostasis appears to be critical for C. jejuni colonization, interventions targeting the AMC could provide a critical control point for therapeutic drug options to combat this zoonotic pathogen. Our results also indicate that even for conserved sRNAs such as CjNC110, strain-specific differences in phenotypes regulated by sRNAs may exist, independent of conserved regulatory action. Depending on the strain examined and accessory genomic content present, conserved regulatory actions might be masked, thus investigation in multiple strains may be warranted.

Identification of RNA-binding protein genes associated with renal rejection and graft survival

Rejection is one of the major factors affecting the long-term prognosis of kidney transplantation, and timely recognition and aggressive treatment of rejection is essential to prevent disease progression. RBPs are proteins that bind to RNA to form ribonucleoprotein complexes, thereby affecting RNA stability, processing, splicing, localization, transport, and translation, which play a key role in post-transcriptional gene regulation. However, their role in renal transplant rejection and long-term graft survival is unclear. The aim of this study was to comprehensively analyze the expression of RPBs in renal rejection and use it to construct a robust prediction strategy for long-term graft survival. The microarray expression profiles used in this study were obtained from GEO database. In this study, a total of eight hub RBPs were identified, all of which were upregulated in renal rejection samples. Based on these RBPs, the renal rejection samples could be categorized into two different clusters (cluster A and cluster B). Inflammatory activation in cluster B and functional enrichment analysis showed a strong association with rejection-related pathways. The diagnostic prediction model had a high diagnostic accuracy for T cell mediated rejection (TCMR) in renal grafts (area under the curve = 0.86). The prognostic prediction model effectively predicts the prognosis and survival of renal grafts (p < .001) and applies to both rejection and non-rejection situations. Finally, we validated the expression of hub genes, and patient prognosis in clinical samples, respectively, and the results were consistent with the above analysis.

MiR-134-3p Regulates Cell Proliferation and Apoptosis by Targeting INHBA via Inhibiting the TGF-β/PI3K/AKT Pathway in Sheep Granulosa Cells.

Inhibin β-A (INHBA), a TGF-β superfamily member, is crucial for developing follicles. Although miRNAs are essential for post-transcriptional gene regulation, it is not yet known how they affect the expression of INHBA during follicle development. Using bioinformatics analyses, miR-134-3p was found, in this investigation, to be a crucial microRNA that targets INHBA in sheep GCs. Furthermore, when the follicular diameter expanded, there was a discernible decline in miR-134-3p expression. The miR-134-3p overexpression markedly reduced the proliferation of GCs, whereas its knockdown augmented it. Moreover, cell cycle progression was enhanced by miR-134-3p overexpression. Furthermore, miR-134-3p overexpression heightened GC apoptosis, while its knockdown reduced it. Importantly, miR-134-3p overexpression blocked the PI3K/AKT/mTOR axis, whereas its knockdown stimulated it. Overall, the outcomes of transfections with INHBA and miR-134-3p showed that, in sheep GCs, miR-134-3p targets INHBA to control cell proliferation and apoptosis. In summary, these results add to our understanding of the molecular mechanisms involving important miRNAs in ewe fecundity by indicating that miR-134-3p influences cell proliferation, cell apoptosis, and the TGF-β/PI3K/AKT/mTOR axis, which, in turn, influences the follicular development of sheep GCs.

ProQ-associated small RNAs control motility in Vibrio cholerae.

Gene regulation at the post-transcriptional level is prevalent in all domains of life. In bacteria, ProQ-like proteins have emerged as important RNA chaperones facilitating RNA stability and RNA duplex formation. In the major human pathogen Vibrio cholerae, post-transcriptional gene regulation is key for virulence, biofilm formation, and antibiotic resistance, yet the role of ProQ has not been studied. Here, we show that ProQ interacts with hundreds of transcripts in V. cholerae, including the highly abundant FlaX small RNA (sRNA). Global analyses of RNA duplex formation using RIL-Seq (RNA interaction by ligation and sequencing) revealed a vast network of ProQ-assisted interactions and identified a role for FlaX in motility regulation. Specifically, FlaX base-pairs with multiple sites on the flaB flagellin mRNA, preventing 30S ribosome binding and translation initiation. V. cholerae cells lacking flaX display impaired motility gene expression, altered flagella composition and reduced swimming in liquid environments. Our results provide a global view on ProQ-associated RNA duplex formation and pinpoint the mechanistic and phenotypic consequences associated with ProQ-associated sRNAs in V. cholerae.

Cancer mutations rewire the RNA methylation specificity of METTL3-METTL14.

Chemical modification of RNAs is important for posttranscriptional gene regulation. The METTL3-METTL14 complex generates most N6-methyladenosine (m6A) modifications in messenger RNAs (mRNAs), and dysregulated methyltransferase expression has been linked to cancers. Here we show that a changed sequence context for m6A can promote oncogenesis. A gain-of-function missense mutation from patients with cancer, METTL14R298P, increases malignant cell growth in culture and transgenic mice without increasing global m6A levels in mRNAs. The mutant methyltransferase preferentially modifies noncanonical sites containing a GGAU motif, in vitro and in vivo. The m6A in GGAU context is detected by the YTH family of readers similarly to the canonical sites but is demethylated less efficiently by an eraser, ALKBH5. Combining the biochemical and structural data, we provide a model for how the cognate RNA sequences are selected for methylation by METTL3-METTL14. Our work highlights that sequence-specific m6A deposition is important and that increased GGAU methylation can promote oncogenesis.

RNA-binding proteins in disease etiology: Fragile X Syndrome and Spinal Muscular Atrophy.

All RNAs exist in complexes (RNPs) with RNA-binding proteins (RBPs). Studies in my lab since the 1980s, identified, sequenced and characterized the major pre-mRNA- and mRNA-RBPs (hnRNPs/mRNPs), revealing RNA-binding domains and common features of numerous RBPs and their central roles in post-transcriptional gene regulation. The first links between RBPs and RNPs to diseases emerged serendipitously for fragile X syndrome, as its gene (FMR1) encoded RBP (FMRP), and spinal muscular atrophy (SMA), caused by deficits in survival motor neurons (SMN). Discoveries of the SMN complex and its unanticipated function in RNP assembly, essential for spliceosomal snRNPs biogenesis, advanced understanding of RNA biology and pathogenesis. I reflect on how these and other contributions (e.g., nucleo-cytoplasmic shuttling; telescripting) originated from curiosity-driven exploration and highly collaborative lab culture. The vast RNA and RBP assortments are beneficial, but increase complexity and chances of disorders, making the RNP sphere a rich source for future discoveries.

InPAS: An R/Bioconductor Package for Identifying Novel Polyadenylation Sites and Alternative Polyadenylation from Bulk RNA-seq Data.

Alternative cleavage and polyadenylation (APA) is a crucial post-transcriptional gene regulation mechanism that regulates gene expression in eukaryotes by increasing the diversity and complexity of both the transcriptome and proteome. Despite the development of more than a dozen experimental methods over the last decade to identify and quantify APA events, widespread adoption of these methods has been limited by technical, financial, and time constraints. Consequently, APA remains poorly understood in most eukaryotes. However, RNA sequencing (RNA-seq) technology has revolutionized transcriptome profiling and recent studies have shown that RNA-seq data can be leveraged to identify and quantify APA events. To fully capitalize on the exponentially growing RNA-seq data, we developed InPAS (Identification of Novel alternative PolyAdenylation Sites), an R/Bioconductor package for accurate identification of novel and known cleavage and polyadenylation sites (CPSs), as well as quantification of APA from RNA-seq data of various experimental designs. Compared to other APA analysis tools, InPAS offers several important advantages, including the ability to detect both novel proximal and distal CPSs, to fine tune positions of CPSs using a naïve Bayes classifier based on flanking sequence features, and to identify APA events from RNA-seq data of complex experimental designs using linear models. We benchmarked the performance of InPAS and other leading tools using simulated and experimental RNA-seq data with matched 3'-end RNA-seq data. Our results reveal that InPAS frequently outperforms existing tools in terms of precision, sensitivity, and specificity. Furthermore, we demonstrate its scalability and versatility by applying it to large, diverse RNA-seq datasets. InPAS is an efficient and robust tool for identifying and quantifying APA events using readily accessible conventional RNA-seq data. Its versatility opens doors to explore APA regulation across diverse eukaryotic systems with various experimental designs. We believe that InPAS will drive APA research forward, deepening our understanding of its role in regulating gene expression, and potentially leading to the discovery of biomarkers or therapeutics for diseases.

SMG5, a component of nonsense-mediated mRNA decay, is essential for the mouse spermatogonial differentiation and maintenance.

Mammalian spermatogenesis is a tightly controlled cellular process including spermatogonial development and differentiation, meiosis of spermatocyte, and the morphological specification of haploid spermatozoa, during which the post-transcriptional gene regulations are vital but poorly understood. Nonsense-mediated mRNA decay (NMD), a highly conserved post-transcriptional regulatory mechanism of gene expression in eukaryotes, recently emerges as a licensing mechanism in cell fate transition, including stem cell differentiation and organogenesis. The function of NMD in spermatogonial development remains elusive. Here we found knockout of SMG5, an important component of the NMD machinery, in embryonic germ cells led to the failure of spermatogenesis and male infertility. SMG5 null resulted in defective differentiation and maintenance of spermatogonia, which affected initiation of meiosis, ultimately caused a "Sertoli cell-only" phenotype. Transcriptome analysis revealed that SMG5 loss led to serious defects in NMD with targets features including PTC, long 3' UTR, and 5' uORFs. Furthermore, SMG5 loss downregulates gene transcripts involved in spermatogonia expansion and differentiation. During the spermatogonial differentiation, the deletion of SMG5 led to hyperactivation of the p38 MAPK signaling pathway, which triggered widespread cell death. These results suggest that SMG5 mediated NMD plays an important role in spermatogenesis by regulating the p38 MAPK signaling pathway.

Pivotal Role of miRNA-lncRNA Interactions in Human Diseases.

New technologies have shown that most of the genome comprises transcripts that cannot code for proteins and are referred to as non-coding RNAs (ncRNAs). Some ncRNAs, like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), are of substantial interest because of their critical function in controlling genes and numerous biological activities. The expression levelsand function of miRNAs and lncRNAs are rigorously monitored throughout developmental processes and the maintenance of physiological homeostasis. Due to their critical roles, any dysregulation or changes in their expression can significantly influence the pathogenesis of various human diseases. The interactions between miRNAs and lncRNAs have been found to influence gene expression in various ways. These interactions significantly influence the understanding of disease etiology, cellular processes, and potential therapeutic targets. Different experimental and in silico methods can be used to investigate miRNA-lncRNA interactions. By aiding the elucidation of miRNA-lncRNA interactions and deepening the understanding of post-transcriptional gene regulation, researchers can open a new window for designing hypotheses, conducting experiments, and discovering methods for diagnosing and treating complex human diseases. This review briefly summarizes miRNA and lncRNA functions, discusses their interaction mechanisms, and examines the experimental and computational methods used to study these interactions. Additionally, we highlight significant studies on lncRNA and miRNA interactions in various diseases from 2000 to 2024, using the academic research databases such as PubMed, Google Scholar, ScienceDirect, and Scopus.

Somatic piRNA and PIWI-mediated post-transcriptional gene regulation in stem cells and disease

PIWI-interacting RNAs (piRNAs) are small non-coding RNAs that bind to the PIWI subclass of the Argonaute protein family and are essential for maintaining germline integrity. Initially discovered in Drosophila, PIWI proteins safeguard piRNAs, forming ribonucleoprotein (RNP) complexes, crucial for regulating gene expression and genome stability, by suppressing transposable elements (TEs). Recent insights revealed that piRNAs and PIWI proteins, known for their roles in germline maintenance, significantly influence mRNA stability, translation and retrotransposon silencing in both stem cells and bodily tissues. In the current review, we explore the multifaceted roles of piRNAs and PIWI proteins in numerous biological contexts, emphasizing their involvement in stem cell maintenance, differentiation, and the development of human diseases. Additionally, we discussed the up-and-coming animal models, beyond the classical fruit fly and earthworm systems, for studying piRNA-PIWIs in self-renewal and cell differentiation. Further, our review offers new insights and discusses the emerging roles of piRNA-dependent and independent functions of PIWI proteins in the soma, especially the mRNA regulation at the post-transcriptional level, governing stem cell characteristics, tumor development, and cardiovascular and neurodegenerative diseases.

Mechanism and function of CEACAM1 splice isoforms.

Alternative splicing is a fundamental mechanism in the post-transcriptional regulation of genes. The multifunctional transmembrane glycoprotein receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) undergoes extensive alternative splicing to allow for tunable functions in cell signalling, adhesion and modulation of immune and metabolic responses. Splice isoforms that differ in their ectodomain and short or long cytoplasmic tail (CEACAM1-S/CEACAM1-L) have distinct functional roles. The mechanisms that regulate CEACAM1 RNA splicing remain elusive. This narrative review summarizes the current knowledge of the mechanism and function of CEACAM1 splice isoforms. Historical perspectives address the biological significance of the glycosylated Ig domains, the variable exon 7, and phosphorylation events that dictate its signal transduction pathways. The use of small antisense molecules to target mis-spliced variable exon 7 is discussed. The Ig variable-like N domain mediates cell adhesion and immune checkpoint inhibitory functions. Gly and Tyr residues in the transmembrane (TM) domain are essential for dimerization. Calmodulin, Calcium/Calmodulin-dependent protein kinase II delta (CamK2D), Actin and Annexin A2 are binding partners of CEACAM1-S. Homology studies of the muCEACAM1-S and huCEACAM1-S TM predict differences in their signal transduction pathways. Hypoxia-inducible factor 1-α (HIF-1-α) induces alternative splicing to produce CEACAM1-S under limited oxygen conditions. Antisense small molecules directed to exon 7 may correct faulty expression of the short and long cytoplasmic tail splicing isoforms. More pre-clinical and clinical studies are needed to elucidate the precise mechanisms by which CEACAM1 RNA splicing may be exploited to develop targeted interventions towards novel therapeutic strategies.

Deciphering the prognostic landscape of triple-negative breast cancer: A focus on immune-related hub genes and therapeutic implications.

Triple-negative breast cancer (TNBC), known for its hostile nature and limited treatment modalities, has spurred researchers to explore novel approaches for enhancing clinical outcomes. Here, the study aimed to analyze transcriptomics data to identify immune-related hub genes associated with TNBC that might serve as prognostic biomarkers. Initially, we determined genes that were differentially expressed between TNBC and normal tissues by integrating microarray and RNA sequencing data. Then, through protein-protein interaction and module analysis, we identified five putative hub genes: AURKA, CCNB1, CDCA8, GAPDH, and TOP2A. Subsequently, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the hub genes were primarily involved in the progesterone-mediated oocyte maturation signaling pathway and oocyte meiosis. Additionally, we observed that these five hub genes were significantly elevated at both protein and mRNA levels in TNBC tissues and contributed to worse survival. Furthermore, the expression of these hub genes exhibited a strong positive association with immune-invading cells such as CD8 T cells, CD4 T cells, and dendritic cells. The analysis of the regulatory network revealed three transcription factors (YBX-1, E2F1, and E2F3) and three posttranscriptional regulators (hsa-mir-25-3p, hsa-mir-92a-3p, and hsa-let-7b-5p) of hub genes. Finally, we explored potential drug candidates for the hub genes using Drug-Gene Interaction Database and discovered that there are no FDA-approved drugs for CCNB1 and CDCA8, highlighting a promising area for future research. Taken together, our results will be of immense importance in addressing the intricacies of TNBC.

Unveiling RNA structure-mediated regulations of RNA stability in wheat

Despite the critical role of mRNA stability in post-transcriptional gene regulation, research on this topic in wheat, a vital agricultural crop, remains unclear. Our study investigated the mRNA decay landscape of durum wheat (Triticum turgidum L. ssp. durum, BBAA), revealing subgenomic asymmetry in mRNA stability and its impact on steady-state mRNA abundance. Our findings indicate that the 3’ UTR structure and homoeolog preference for RNA structural motifs can influence mRNA stability, leading to subgenomic RNA decay imbalance. Furthermore, single-nucleotide variations (SNVs) selected for RNA structural motifs during domestication can cause variations in subgenomic mRNA stability and subsequent changes in steady-state expression levels. Our research on the transcriptome stability of polyploid wheat highlights the regulatory role of non-coding region structures in mRNA stability, and how domestication shaped RNA structure, altering subgenomic mRNA stability. These results illustrate the importance of RNA structure-mediated post-transcriptional gene regulation in wheat and pave the way for its potential use in crop improvement.

The 2024 Nobel prize in Medicine: impact on hemostasis and thrombosis research

On October 7th, the Nobel Prize in Physiology or Medicine was awarded jointly to Victor Ambros and Gary Ruvkun for the discovery of microRNA and its role in post-transcriptional gene regulation...

Dengue virus NS1 hits hard at the barrier integrity of human cerebral microvascular endothelial cells via cellular microRNA dysregulations

ABSTRACT Dengue virus (DENV) infections are commonly reported in the tropical and subtropical regions of the world. DENV is reported to exploit various strategies to cross the blood-brain barrier. The NS1 protein of DENV plays an important role in viral neuropathogenesis, resulting in endothelial hyperpermeability and cytokine-induced vascular leak. miRNAs are short non-coding RNAs that play an important role in post-transcriptional gene regulations. However, no comprehensive information about the involvement of miRNAs in DENV-NS1-mediated neuropathogenesis has been explored to date. We observed that DENV-NS1 significantly alters the cellular miRNome of human cerebral microvascular endothelial cells in a bystander fashion. Subsequent target prediction and pathway enrichment analysis indicated that these microRNAs and their corresponding target genes are involved in pathways associated with blood-brain barrier dysfunction such as “Adherens junction” and “Tight junction”. Additionally, several miRNA-mRNA pairs were also found to be involved in cellular signaling pathways related to cytokine production, for instance, “Jak-STAT signaling pathway”, “Chemokine signaling pathway”, “IL-17 signaling pathway”, “NF-κB signaling pathway”, and “Viral protein interaction with cytokine and cytokine receptor”. The dysregulated production of inflammatory cytokines is reported to compromise BBB permeability. This study is the first report to demonstrate that DENV-NS1-mediated miRNA perturbations are crucial in compromising endothelial barrier integrity. It also offers insights into potential therapeutic targets to mitigate DENV-NS1-induced vascular permeability and inflammation.

Characterizing Host microRNA: Virus Interactions of Orthoavulavirus javaense.

Post-transcriptional gene regulation mediated by microRNAs (miRNAs) relies on sequence complementarity between the miRNA seed site and the target gene transcript(s). This complementarity can completely inhibit or reduce translation into protein. We hypothesized that viruses employ sequence complementarity/similarity with host miRNAs to inhibit or increase the miRNA-mediated regulation of host gene expression specifically during viral infection(s). In this study, we focus on Orthoavulavirus javaense (OAVJ), the causative of Newcastle disease, a poultry disease with significant economic impact. A computational analysis of OAVJ genomes from low-virulence (lentogenic) versus virulent (velogenic) viruses was carried out to identify viral signature motifs that potentially either mimic or complement host miRNA seed sequences. Data show that OAVJ genomes harbor viral seed mimics (vSMs) or viral seed sponges (vSSs) and can mimic host miRNAs or inhibit their regulation of host genes, disrupting cellular pathways. Our analyses showed that velogens encode a statistically significant higher number of vSMs and a lower number of vSSs relative to lentogens. The number of vSMs or vSSs did not correlate with gene length. The analysis of the secondary structures flanking these vSMs and vSSs showed structural features common to miRNA precursors. The inhibition or upregulation of vSS-miR-27b-5p altered P gene expression in a sequence-dependent manner. These data demonstrate that viral transcripts can interact with host miRNAs to alter the outcomes of infection.

A Thorough Navigation of miRNA's Blueprint in Crafting Cardiovascular Fate.

Cardiovascular diseases contribute significantly to global morbidity and mortality. MicroRNAs are crucial in the development and progression of these diseases by regulating gene expression in various cells and tissues. Their roles in conditions like atherosclerosis, heart failure, myocardial infarction, and arrhythmias have been widely researched. The present study provides an overview of existing evidence regarding miRNAs' role in cardiovascular disease pathogenesis. Furthermore, the study examines current state-of-the-art technologies used in the study of miRNAs in cardiovascular disease. As a final point, we examine how miRNAs may serve as disease biomarkers, therapeutic targets, and prognostic indicators. In cardiology, microRNAs, small noncoding RNA molecules, are crucial to the posttranscriptional regulation of genes. Their role in regulating cardiac cell differentiation and maturation is critical during the development of the heart. They maintain the cardiac function of an adult heart by contributing to its electrical and contractile activity. By binding to messenger RNA molecules, they inhibit protein translation or degrade mRNA. Several cardiovascular diseases are associated with dysregulation of miRNAs, including arrhythmias, hypertension, atherosclerosis, and heart failure. miRNAs can be used as biomarkers to diagnose and predict diseases as well as therapeutic targets. A variety of state-of-the-art technologies have aided researchers in discovering, profiling, and analyzing miRNAs, including microarray analysis, next-generation sequencing, and others. Developing new diagnostics and therapeutic approaches is becoming more feasible as researchers refine their understanding of miRNA function. Ultimately, this will reduce the burden of cardiovascular disease around the world.

Unravelling alternative splicing patterns in susceptible and resistant Brassica napus lines in response to Xanthomonas campestris infection

BackgroundRapeseed (Brassica napus L.) is an important oil and industrial crop worldwide. Black rot caused by the bacterial pathogen Xanthomonas campestris pv. campestris (Xcc) is an infectious vascular disease that leads to considerable yield losses in rapeseed. Resistance improvement through genetic breeding is an effective and sustainable approach to control black rot disease in B. napus. However, the molecular mechanisms underlying Brassica-Xcc interactions are not yet fully understood, especially regarding the impact of post-transcriptional gene regulation via alternative splicing (AS).ResultsIn this study, we compared the AS landscapes of a susceptible parental line and two mutagenized B. napus lines with contrasting levels of black rot resistance. Different types of AS events were identified in these B. napus lines at three time points upon Xcc infection, among which intron retention was the most common AS type. A total of 1,932 genes was found to show differential AS patterns between different B. napus lines. Multiple defense-related differential alternative splicing (DAS) hub candidates were pinpointed through an isoform-based co-expression network analysis, including genes involved in pathogen recognition, defense signalling, transcriptional regulation, and oxidation reduction.ConclusionThis study provides new insights into the potential effects of post-transcriptional regulation on immune responses in B. napus towards Xcc attack. These findings could be beneficial for the genetic improvement of B. napus to achieve durable black rot resistance in the future.