Post-transcriptional Level Research Articles

Long non-coding RNA (LncRNA) and epigenetic factors: their role in regulating the adipocytes in bovine.

Investigating the involvement of long non-coding RNAs (lncRNAs) and epigenetic processes in bovine adipocytes can provide valuable new insights into controlling adipogenesis in livestock. Long non-coding RNAs have been associated with forming chromatin loops that facilitate enhancer-promoter interactions during adipogenesis, as well as regulating important adipogenic transcription factors like C/EBPα and PPARγ. They significantly influence gene expression regulation at the post-transcriptional level and are extensively researched for their diverse roles in cellular functions. Epigenetic modifications such as chromatin reorganization, histone alterations, and DNA methylation subsequently affect the activation of genes related to adipogenesis and the progression of adipocyte differentiation. By investigating how fat deposition is epigenetically regulated in beef cattle, scientists aim to unravel molecular mechanisms, identify key regulatory genes and pathways, and develop targeted strategies for modifying fat deposition to enhance desirable traits such as marbling and meat tenderness. This review paper delves into lncRNAs and epigenetic factors and their role in regulating bovine adipocytes while focusing on their potential as targets for genetic improvement to increase production efficiency. Recent genomics advancements, including molecular markers and genetic variations, can boost animal productivity, meeting global demands for high-quality meat products. This review establishes a foundation for future research on understanding regulatory networks linked to lncRNAs and epigenetic changes, contributing to both scholarly knowledge advancement and practical applications within animal agriculture.

CFTR Exon 10 deleterious mutations in patients with congenital bilateral absence of vas deferens in a cohort of Pakistani patients.

Congenital bilateral absence of vas deferens (CBAVD) is a urological syndrome of Wolffian ducts and is responsible for male infertility and obstructive azoospermia. This study is designed to explore the integrity of exon 10 of CFTR and its role in male infertility in a cohort of CBVAD patients in Pakistan. Genomic DNA was extracted from 17 male patients with CBAVD having clinical symptoms, and 10 healthy controls via phenol-chloroform method. Exon 10 of the CFTR gene was amplified, using PCR with specific primers and DNA screening was done by Sanger sequencing. Sequencing results were analyzed using freeware Serial Cloner, SnapGene, BioEdit and FinchTV. Furthermore, bioinformatics tools were used to analyze the mutations and their impact on the protein function and stability. We have identified 4 mutations on exon 10 of CFTR in 6 out of 17 patients. Two of the mutations were missense variants V456A, K464E, and the other two were silent mutations G437G, S431S. The identified variant V456A was present in 4 of the studied patients. Whereas, the presence of K464E in our patients further weighs on the crucial importance for its strategic location to influence the gene function at post-transcriptional and protein level. Furthermore, Polyphen-2 and SIFT analyze the mutations as harmful and deleterious. The recurrence of V456A and tactically conserved locality of K464E are evidence of their potential role in CBAVD patients and in male infertility. The data can contribute in developing genetic testing and treatment of CBAVD.

IGFBP7 regulates cell proliferation and migration through JAK/STAT pathway in gastric cancer and is regulated by DNA and RNA methylation.

New biomarkers for early diagnosis of gastric cancer (GC), the second leading cause of cancer-related death, are urgently needed. IGFBP7, known to play various roles in multiple tumours, is complexly regulated across diverse cancer types, as evidenced by our pancancer analysis. Bioinformatics analysis revealed that IGFBP7 expression was related to patient prognosis, tumour clinicopathological characteristics, tumour stemness, microsatellite instability and immune cell infiltration, as well as the expression of oncogenes and immune checkpoints. GSEA links IGFBP7 to several cancer-related pathways. IGFBP7 deficiency inhibited GC cell proliferation and migration invitro. Furthermore, an invivo nude mouse model revealed that IGFBP7 downregulation suppressed the tumorigenesis of GC cells. Western blotting analysis showed that the JAK1/2-specific inhibitor ruxolitinib could rescue alterations induced by IGFBP7 overexpression in GC cells. Additionally, our bioinformatics analysis and invitro assays suggested that IGFBP7 is regulated by DNA methylation at the genetic level and that the RNA m6A demethylase FTO modulates it at the posttranscriptional level. This study emphasizes the clinical relevance of IGFBP7 in GC and its influence on cell proliferation and migration via the JAK/STAT signalling pathway. This study also highlights the regulation of IGFBP7 in GC by DNA and m6A RNA methylation.

Non-coding RNAs as Key Regulators of the Notch Signaling Pathway in Glioblastoma: Diagnostic, Prognostic, and Therapeutic Targets.

Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.

CEP112 coordinates translational regulation of essential fertility genes during spermiogenesis through phase separation in humans and mice

Spermiogenesis, the complex transformation of haploid spermatids into mature spermatozoa, relies on precise spatiotemporal regulation of gene expression at the post-transcriptional level. The mechanisms underlying this critical process remain incompletely understood. Here, we identify centrosomal protein 112 (CEP112) as an essential regulator of mRNA translation during this critical developmental process. Mutations in CEP112 are discovered in oligoasthenoteratospermic patients, and Cep112-deficient male mice recapitulate key phenotypes of human asthenoteratozoospermia. CEP112 localizes to the neck and atypical centrioles of mature sperm and forms RNA granules during spermiogenesis, enriching target mRNAs such as Fsip2, Cfap61, and Cfap74. Through multi-omics analyses and the TRICK reporter assay, we demonstrate that CEP112 orchestrates the translation of target mRNAs. Co-immunoprecipitation and mass spectrometry identify CEP112’s interactions with translation-related proteins, including hnRNPA2B1, EEF1A1, and EIF4A1. In vitro, CEP112 undergoes liquid-liquid phase separation, forming condensates that recruit essential proteins and mRNAs. Moreover, variants in patient-derived CEP112 disrupt phase separation and impair translation efficiency. Our results suggest that CEP112 mediates the assembly of RNA granules through liquid-liquid phase separation to control the post-transcriptional expression of fertility-related genes. This study not only clarifies CEP112’s role in spermatogenesis but also highlights the role of phase separation in translational regulation, providing insights into male infertility and suggesting potential therapeutic targets.

Silencing Osa-miR827 via CRISPR/Cas9 protects rice against the blast fungus Magnaporthe oryzae

MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression at the post-transcriptional level. In plants, miRNAs participate in diverse developmental processes and adaptive responses to biotic and abiotic stress. MiR827 has long been recognized to be involved in plant responses to phosphate starvation. In rice, the miR827 regulates the expression of OsSPX-MFS1 and OsSPX-MFS2, these genes encoding vacuolar phosphate transporters. In this study, we demonstrated that miR827 plays a role in resistance to infection by the fungus Magnaporthe oryzae in rice. We show that MIR827 overexpression enhances susceptibility to infection by M. oryzae which is associated to a weaker induction of defense gene expression during pathogen infection. Conversely, CRISPR/Cas9-induced mutations in the MIR827 gene completely abolish miR827 production and confer resistance to M. oryzae infection. This resistance is accompanied by a reduction of leaf Pi content compared to wild-type plants, whereas Pi levels increase in leaves of the blast-susceptible miR827 overexpressor plants. In wild-type plants, miR827 accumulation in leaves decreases during the biotrophic phase of the infection process. Taken together, our data indicates that silencing MIR827 confers resistance to M. oryzae infection in rice while further supporting interconnections between Pi signaling and immune signaling in plants. Unravelling the role of miR827 during M. oryzae infection provides knowledge to improve blast resistance in rice by CRISPR/Cas9-editing of MIR827.

Modern Plant Breeding Techniques in Crop Improvement and Genetic Diversity: From Molecular Markers and Gene Editing to Artificial Intelligence—A Critical Review

With the development of new technologies in recent years, researchers have made significant progress in crop breeding. Modern breeding differs from traditional breeding because of great changes in technical means and breeding concepts. Whereas traditional breeding initially focused on high yields, modern breeding focuses on breeding orientations based on different crops’ audiences or by-products. The process of modern breeding starts from the creation of material populations, which can be constructed by natural mutagenesis, chemical mutagenesis, physical mutagenesis transfer DNA (T-DNA), Tos17 (endogenous retrotransposon), etc. Then, gene function can be mined through QTL mapping, Bulked-segregant analysis (BSA), Genome-wide association studies (GWASs), RNA interference (RNAi), and gene editing. Then, at the transcriptional, post-transcriptional, and translational levels, the functions of genes are described in terms of post-translational aspects. This article mainly discusses the application of the above modern scientific and technological methods of breeding and the advantages and limitations of crop breeding and diversity. In particular, the development of gene editing technology has contributed to modern breeding research.

Characterization of the AGR2-NPM3 axis uncovers the AGR2 involvement in PD-L1 regulation in colorectal cancer

Despite extensive research, the molecular role of AGR2 in the progression and metastasis of colorectal cancer (CRC) has not been fully characterized. We used quantitative mass spectrometry (SWATH MS) to identify differentially expressed proteins in paired CRC cell models of the SW480 and SW620 cell lines in response to AGR2 protein level manipulation. Relying on the results from SWATH MS and subsequent immunochemical validation, we selected NMP3 as the top candidate protein associated with AGR2 in CRC tumour cells in our screen. RT‒qPCR and immunochemical analysis confirmed the involvement of AGR2-mediated regulation of NPM3 at the transcriptional and posttranscriptional levels. Since PD-L1 is a constituent of the NPM3 regulatory axis, we aimed to correlate the changes in PD-L1 to the differential expression of AGR2 in our cell models. We found that AGR2 positively regulates PD-L1 levels in both SW480 and SW620 cell lines; additionally, several different CRC patient transcriptome cohorts confirmed the association of AGR2 with PD-L1. Our work reveals a new AGR2-NPM3 regulatory axis and the involvement of AGR2 in the regulation of PD-L1, which paves the way for the association of AGR2 with immune evasion in CRC cells.

A virulence-associated small RNA MTS1338 activates an ABC transporter CydC for rifampicin efflux in Mycobacterium tuberculosis.

The efficacy of the tuberculosis treatment is restricted by innate drug resistance of Mycobacterial tuberculosis and its ability to acquire resistance to all anti-tuberculosis drugs in clinical use. A profound understanding of bacterial ploys that decrease the effectiveness of drugs would identify new mechanisms for drug resistance, which would subsequently lead to the development of more potent TB therapies. In the current study, we identified a virulence-associated small RNA (sRNA) MTS1338-driven drug efflux mechanism in M. tuberculosis. The treatment of a frontline antitubercular drug rifampicin upregulated MTS1338 by >4-fold. Higher intrabacterial abundance of MTS1338 increased the growth rate of cells in rifampicin-treated conditions. This fact was attributed by the upregulation of an efflux protein CydC by MTS1338. Gel-shift assay identified a stable interaction of MTS1338 with the coding region of cydC mRNA thereby potentially stabilizing it at the posttranscriptional level. The drug efflux measurement assays revealed that cells with higher MTS1338 abundance accumulate less drug in the cells. This study identified a new regulatory mechanism of drug efflux controlled by an infection-induced sRNA in M. tuberculosis.

Identification and function of microRNAs in hemipteran pests: A review.

Hemiptera is one of the most significant orders of insect pests, including whiteflies, true bugs, aphids, planthoppers, psyllids, and so forth, which have led to substantial economic losses in agricultural industries and have significantly affected food yields through their ability to suck the phloem sap of crops and transmit numerous bacterial and viral pathogens. Therefore, explorations of pest-specific, eco-friendly and easy-to-adopt technologies for hemipteran pest control are urgently needed. To the best of our knowledge, microRNAs (miRNAs), which are endogenous non-coding small RNAs approximately 22 nucleotides in length, are involved in regulating gene expression via the direct recognition and binding of the 3'-untranslated region (3'-UTR) of target messenger RNAs (mRNAs) or by acting as a center of a competitive endogenous RNA (ceRNA) network at the post-transcriptional level. This review systematically outlines the characterization and functional investigation of the miRNA biogenesis pathway in hemipteran pests, such as whiteflies, true bugs, aphids and planthoppers. In addition, we explored the results of small RNA sequencing and functional observations of miRNAs in these pests, and the results suggest that the numerous miRNAs obtained and annotated via high-throughput sequencing technology and bioinformatic analyses contribute to molting development, fitness, wing polyphenism, symbiont interactions and insecticide resistance in hemipteran pests. Finally, we summarize current advances and propose a framework for future research to extend the current data and address potential limitations in the investigation and application of hemipteran miRNAs.

Contribution of A1 to macrophage survival in cooperation with MCL-1 and BCL-XL in a murine cell model of myeloid differentiation

Myeloid cells are the first line of defence against pathogens. Mitochondrial apoptosis signalling is a crucial regulator of myeloid cell lifespan and modulates the function of myeloid cells. The anti-apoptotic protein BCL-2-family protein BCL2A1/A1/BFL-1 is strongly upregulated in inflammation in macrophages. We analysed the contribution of A1 to apoptosis regulation in a conditional system of in vitro differentiation of murine macrophages from immortalised progenitors. We disabled the expression of A1 by targeting all murine A1 isoforms in the genome. Specific inhibitors were used to inactivate other anti-apoptotic proteins. Macrophage progenitor survival mainly depended on the anti-apoptotic proteins MCL-1, BCL-XL and A1 but not BCL-2. Deletion of A1 on its own had little effect on progenitor cell survival but was sensitised to cell death induction when BCL-XL or MCL-1 was neutralised. In progenitors, A1 was required for survival in the presence of the inflammatory stimulus LPS. Differentiated macrophages were resistant to inhibition of single anti-apoptotic proteins, but A1 was required to protect macrophages against inhibition of either BCL-XL or MCL-1; BCL-2 only had a minor role in these cells. Cell death by neutralisation of anti-apoptotic proteins completely depended on BAX with a small contribution of BAK only in progenitors in the presence of LPS. A1 and NOXA appeared to stabilise each other at the posttranscriptional level suggesting direct binding. Co-immunoprecipitation experiments showed the binding of A1 to NOXA and BIM. Interaction between A1 and Noxa may indirectly prevent neutralisation and destabilization of MCL-1. Our findings suggest a unique role for A1 as a modulator of survival in the macrophage lineage in concert with MCL-1 and BCL-XL, especially in a pro-inflammatory environment.

Non-redundant roles for the human mRNA decapping cofactor paralogs DCP1a and DCP1b.

Eukaryotic gene expression is regulated at the transcriptional and post-transcriptional levels, with disruption of regulation contributing significantly to human diseases. The 5' m7G mRNA cap is a central node in post-transcriptional regulation, participating in both mRNA stabilization and translation efficiency. In mammals, DCP1a and DCP1b are paralogous cofactor proteins of the mRNA cap hydrolase DCP2. As lower eukaryotes have a single DCP1 cofactor, the functional advantages gained by this evolutionary divergence remain unclear. We report the first functional dissection of DCP1a and DCP1b, demonstrating that they are non-redundant cofactors of DCP2 with unique roles in decapping complex integrity and specificity. DCP1a is essential for decapping complex assembly and interactions between the decapping complex and mRNA cap-binding proteins. DCP1b is essential for decapping complex interactions with protein degradation and translational machinery. DCP1a and DCP1b impact the turnover of distinct mRNAs. The observation that different ontological groups of mRNA molecules are regulated by DCP1a and DCP1b, along with their non-redundant roles in decapping complex integrity, provides the first evidence that these paralogs have qualitatively distinct functions.

Clo-miR-14: a medicinally valued spice-derived miRNA with therapeutic implications in rheumatoid arthritis.

Plant microRNAs (miRNA) are regularly consumed orally along with diet, gaining attention for their RNA-based drug potential because of their ability to regulate mammalian gene expression specifically at the post-transcriptional level. Medicinally valued plants are well known for their anti-inflammatory property; however, the contribution of their miRNA in managing inflammation has been less studied. We investigated miRNA from four medicinally valued regularly consumed spices, and validated one of the most potential miRNA 'Clo-miR-14' for its thermal stability, and absorption in the plasma samples of RA patient's by RT-PCR. In vitro and in vivo studies were performed to investigate the effect of Clo-miR-14 in ameliorating rheumatoid arthritis (RA) like symptoms. Our results suggest that 'Clo-miR-14,' an exogenous miRNA present in Curcuma longa, absorbed through regular diet, has robust thermal stability at 100°C in humans. It significantly reduced pro-inflammatory cytokines (TNF, IL-1β, IL-6) and RA-like symptoms, suggesting that plant-based miRNA could be a promising candidate as an RNA-based drug for RA pathogenesis.

MiR-927 regulates insect wing development by targeting the Hippo pathway.

How organ size is determined is a fundamental question in life sciences. Recent studies have highlighted the importance of the Hippo pathway in regulating organ size. This pathway controls cell proliferation and cell death to maintain the proper number of cells. The activity of the Hippo pathway is tightly fine-tuned through various post-translational modifications, such as phosphorylation and ubiquitination. Here, we discover that miR-927 is a novel regulator of wing size. Overexpression of miR-927 decreases wing size, which can be rescued by co-expressing miR-927-sponge. Next, we show that miR-927 stimulates apoptosis and suppresses the expression of Drosophila inhibitor of apoptosis protein 1, a well-known target gene of the Hippo pathway. Genetic epistatic analyses position miR-927 upstream of Yorkie (Yki) to modulate the Hippo pathway. In addition, there is a matching miR-927 seed site in the yki 3' untranslated region (3'-UTR), and we demonstrate that yki 3'-UTR is the direct target of miR-927. Ultimately, our study reveals that the targeting of yki by miR-927 to regulate the Hippo pathway is conserved in Helicoverpa armigera. Administration of miR-927 via star polycation (SPc) nanocarrier effectively inhibits wing development in H. armigera. Taken together, our findings uncover a novel mechanism by which Yki is silenced at the post-transcriptional level by miR-927, and provide a new perspective on pest management.

DUF1127-containing protein and ProQ had opposite effects on biofilm formation in Vibrio alginolyticus

The RNA binding protein is crucial for gene regulation at the post transcription level. In this study, functions of the DUF1127-containing protein and ProQ, which are RNA-binding proteins, were revealed in Vibrio alginolyticus. DUF1127 deletion increased the ability of biofilm formation, whereas ProQ deletion reduced the amount of biofilm. Moreover, extracellular proteinase secretion was significantly reduced in the DUF1127 deletion strain. ProQ, not DUF1127-containing protein, can help the cell to defense oxidative stress. Deletion of DUF1127 resulted in a higher ROS level in the cell, however, ProQ deletion showed no difference. RNA-seq unveiled the expression of genes involved in extracellular protease secretion were significantly downregulated and biofilm synthesis-related genes, such as rbsB and alsS, were differentially expressed in the DUF1127 deletion strain. ProQ affected the expression of genes involved in biofilm synthesis (flgC and flgE), virulence (betB and hutG), and oxidative stress. Moreover, the DUF1127-containing and ProQ affected the mRNA levels of various regulators, such as LysR and BetI. Overall, our study revealed that the DUF1127-containing protein and ProQ have crucial functions on biofilm formation in V. alginolyticus.

Targeting stress induction of GRP78 by cardiac glycoside oleandrin dually suppresses cancer and COVID-19

BackgroundDespite recent therapeutic advances, combating cancer resistance remains a formidable challenge. The 78-kilodalton glucose-regulated protein (GRP78), a key stress-inducible endoplasmic reticulum (ER) chaperone, plays a crucial role in both cancer cell survival and stress adaptation. GRP78 is also upregulated during SARS-CoV-2 infection and acts as a critical host factor. Recently, we discovered cardiac glycosides (CGs) as novel suppressors of GRP78 stress induction through a high-throughput screen of clinically relevant compound libraries. This study aims to test the possibility that agents capable of blocking stress induction of GRP78 could dually suppress cancer and COVID-19.ResultsHere we report that oleandrin (OLN), is the most potent among the CGs in inhibiting acute stress induction of total GRP78, which also results in reduced cell surface and nuclear forms of GRP78 in stressed cells. The inhibition of stress induction of GRP78 is at the post-transcriptional level, independent of protein degradation and autophagy and may involve translational control as OLN blocks stress-induced loading of ribosomes onto GRP78 mRNAs. Moreover, the human Na+/K+-ATPase α3 isoform is critical for OLN suppression of GRP78 stress induction. OLN, in nanomolar range, enhances apoptosis, sensitizes colorectal cancer cells to chemotherapeutic agents, and reduces the viability of patient-derived colon cancer organoids. Likewise, OLN, suppresses GRP78 expression and impedes tumor growth in an orthotopic breast cancer xenograft model. Furthermore, OLN blocks infection by SARS-CoV-2 and its variants and enhances existing anti-viral therapies. Notably, GRP78 overexpression mitigates OLN-mediated cancer cell apoptotic onset and suppression of virus release.ConclusionOur findings validate GRP78 as a target of OLN anti-cancer and anti-viral activities. These proof-of-principle studies support further investigation of OLN as a readily accessible compound to dually combat cancer and COVID-19.

AMPK-mediated regulation of cardiac energy metabolism: Implications for thermotolerance in Argopecten irradians irradians

AMPK is a key regulator of metabolism in eukaryotes across various pathways related to energy regulation. Although extensive investigations of AMPK have been conducted in mammals and some model organisms, research on AMPK in scallops is comparatively limited. In this study, three AMPK family genes (AiAMPKα, AiAMPKβ and AiAMPKγ) in scallop Argopecten irradians irradians were identified through genome scanning. Structure prediction and phylogenetic analyses of AiAMPKs were performed to determine their structural features and evolutionary relationships. Spatiotemporal expression patterns of AiAMPKs at different developmental stages and in healthy adult tissues were analyzed to elucidate the function of AiAMPKs in bay scallops’ growth and development. The spatiotemporally specific expression of AiAMPKs implied their important roles in growth and development of bay scallops. Heat stress experiment was performed to determine the regulations of AiAMPKs in four kinds of thermosensitive tissues. Expression profiles revealed distinct molecular mechanisms of AiAMPKs in different tissues in response to heat stress: significant down-regulations in mobile hemocytes, but dominant up-regulations occurring in stationary gills, mantles and hearts. Functional verification including knock-down of AiAMPKα and inhibition of AiAMPK was separately conducted in the thermotolerant tissue heart at the post-transcription and translation levels. The thermotolerant index Arrhenius break temperature (ABT) showed a significant decrease and the rate-amplitude product (RAP) peaked earlier in the individuals after RNAi targeting AiAMPKα, displaying an earlier transition to anaerobic metabolism under heat stress, indicating an impairing ability of aerobic metabolism. After AiAMPK inhibition, widespread down-regulations of genes in key energy metabolism pathways, RNA polymerase II-mediated transcription, and aminoacyl-tRNA synthesis pathways were obviously observed, revealing the post-translational inhibition of AiAMPK hindered cardiac energy metabolism, basal transcription and translation. Overall, our findings provide evidences for exploring the molecular mechanisms of energy regulation in thermotolerant traits in bay scallops under ongoing global warming.

Exploring the Role of the Processing Body in Plant Abiotic Stress Response.

The processing body (P-Body) is a membrane-less organelle with stress-resistant functions. Under stress conditions, cells preferentially translate mRNA that favors the stress response, resulting in a large number of transcripts unfavorable to the stress response in the cytoplasm. These non-translating mRNAs aggregate with specific proteins to form P-Bodies, where they are either stored or degraded. The protein composition of P-Bodies varies depending on cell type, developmental stage, and external environmental conditions. This review primarily elucidates the protein composition in plants and the assembly of P-Bodies, and focuses on the mechanisms by which various proteins within the P-Bodies of plants regulate mRNA decapping, degradation, translational repression, and storage at the post-transcriptional level in response to ethylene signaling and abiotic stresses such as drought, high salinity, or extreme temperatures. This overview provides insights into the role of the P-Body in plant abiotic stress responses.

MicroRNAs Regulate the Expression of Genes Related to the Innate Immune and Inflammatory Response in Rabbits Infected with Lagovirus europaeus GI.1 and GI.2 Genotypes.

MicroRNAs (miR) are a group of small, non-coding RNAs of 17-25 nucleotides that regulate gene expression at the post-transcriptional level. Dysregulation of miRNA expression or function may contribute to abnormal gene expression and signaling pathways, leading to disease pathology. Lagovirus europaeus (L. europaeus) causes severe disease in rabbits called rabbit hemorrhagic disease (RHD). The symptoms of liver, lung, kidney, and spleen degeneration observed during RHD are similar to those of acute liver failure (ALF) and multi-organ failure (MOF) in humans. In this study, we assessed the expression of miRs and their target genes involved in the innate immune and inflammatory response. Also, we assessed their potential impact on pathways in L. europaeus infection-two genotypes (GI.1 and GI.2)-in the liver, lungs, kidneys, and spleen. The expression of miRs and target genes was determined using quantitative real-time PCR (qPCR). We assessed the expression of miR-155 (MyD88, TAB2, p65, NLRP3), miR-146a (IRAK1, TRAF6), miR-223 (TLR4, IKKα, NLRP3), and miR-125b (MyD88). We also examined biomarkers of inflammation: IL-1β, IL-6, TNF-α, and IL-18 in four tissues at the mRNA level. Our study shows that the main regulators of the innate immune and inflammatory response in L. europaeus/GI.1 and GI.2 infection, as well as RHD, are miR-155, miR-223, and miR-146a. During infection with L. europaeus/RHD, miR-155 has both pro- and anti-inflammatory effects in the liver and anti-inflammatory effects in the kidneys and spleen; miR-146a has anti-inflammatory effects in the liver, lungs and kidneys; miR-223 has anti-inflammatory effects in all tissues; however, miR-125b has anti-inflammatory effects only in the liver. In each case, such an effect may be a determinant of the pathogenesis of RHD. Our research shows that miRs may regulate three innate immune and inflammatory response pathways in L. europaeus infection. However, the result of this regulation may be influenced by the tissue microenvironment. Our research shows that infection of rabbits with L. europaeus/GI.1 and GI.2 genotypes causes an overexpression of two critical acute phase cytokines: IL-6 in all examined tissues and TNF-α (in the liver, lungs, and spleen). IL-1β was highly expressed only in the lungs after L. europaeus infection. These facts indicate a strong and rapid involvement of the local innate immune and inflammatory response in L. europaeus infection-two genotypes (GI.1 and GI.2)-and in the pathogenesis of RHD. Profile of biomarkers of inflammation in rabbits infected with L. europaeus/GI.1 and GI.2 genotypes are similar regarding the nature of changes but are different for individual tissues. Therefore, we propose three inflammation profiles for L. europaeus infection for both GI.1 and GI.2 genotypes (pulmonary, renal, liver, and spleen).

Ferritin Hinders Ferroptosis in Non-Tumorous Diseases: Regulatory Mechanisms and Potential Consequences.

Ferritin, as an iron storage protein, has the potential to inhibit ferroptosis by reducing excess intracellular free iron concentrations and lipid reactive oxygen species (ROS). An insufficient amount of ferritin is one of the conditions that can lead to ferroptosis through the Fenton reaction mediated by ferrous iron. Consequently, upregulation of ferritin at the transcriptional or posttranscriptional level may inhibit ferroptosis. In this review, we have discussed the essential role of ferritin in ferroptosis and the regulatory mechanism of ferroptosis in ferritin-deficient individuals. The description of the regulatory factors governing ferritin and its properties in regulating ferroptosis as underlying mechanisms for the pathologies of diseases will allow potential therapeutic approaches to be developed.