Piwi-interacting RNAs Research Articles

Seasonal piRNA Expression Profile Changes in the Testes of Plateau Zokor (Eospalax baileyi).

Seasonal reproduction is a mammalian behavior that has developed over an extended evolutionary period and requires animals to respond to external environmental changes to facilitate reproduction. In this study, we investigated the role of PIWI-interacting RNA (piRNA) in the seasonal reproduction of plateau zokors (Eospalax baileyi). piRNA expression profiles in plateau zokor testes during both breeding and non-breeding seasons were examined. The piRNAs had a distinctive ping-pong signature and ranged from 27 to 32 nt with a peak at 30 nt. Testicular piRNAs predominantly aligned to specific genomic regions, including repeat and gene regions. Analysis of the piRNA-mRNA interaction network and functional enrichment of differentially expressed piRNAs targeting mRNAs revealed their association with testicular development and spermatogenesis. Significantly, PIWIL4 is an mRNA gene that interacts with piRNA and exhibits high expression levels within the testes during the non-breeding phase. This study provides a foundation to improve our understanding of piRNA regulatory mechanisms during testicular development and spermatogenesis in seasonally reproducing animals and, specifically, in the plateau zokor.

Intraindividual variability of semen quality, proteome, and sncRNA profiles in a healthy cohort of young adults.

Within-subject variability of semen parameters and molecular components of ejaculates in young men remains poorly understood. To investigate intraindividual variability (IIV) of semen parameters and molecular markers in repeated ejaculates from young men. Semen parameters were assessed in samples collected 6-8 days apart from 164 18-19-year old participants of the Russian Children's Study, a prospective cohort. Subsets of paired samples were used for label-free quantitation and targeted mass-spectrometry of proteins in seminal plasma (SP) and seminal extracellular vesicles (EVs), and for small non-coding RNA (sncRNA) profiling in EVs and spermatozoa using RNA-seq. The mean difference between two ejaculates, within-subject variation, intraclass correlation, and concordance correlation were used to assess IIV for all parameters. Low variability with high reproducibility and high reliability was considered if CVw<15% and ICC>0.90, respectively. Analytical variability was low for all investigated parameters in technical replicates. IIV was assessed for basic semen parameters and proteins in SPs and EVs: 319 and 777 proteins, respectively, using untargeted analysis; 9 and 10 proteins using targeted quantification. We also described the IIV for sncRNA, including microRNA, piwi-interacting RNA, tRNA, and tRNA-derived small RNA (tsRNA) in EVs (409 sncRNA and 78 tsRNA) and in spermatozoa (265 sncRNA and 15 tsRNA). We identified 22 and 27 non-overlapping proteins in SP and EVs, respectively, and 46 and 9 sncRNA, including 5 and 0 tsRNA in seminal EVs and spermatozoa, respectively, with low variability. The fatty acid synthase (FAS) had the lowest IIV in both media in targeted protein quantification. We identified a number of proteins and sncRNA with low variability among 111 proteins, 176 sncRNA, and 12 tsRNA which were previously suggested as biomarkers of male fertility and reproductive outcomes: lactotransferrin, cysteine-rich secretory protein 3, alpha-1-antichymotrypsin, epididymal sperm-binding protein 1, glutathione S-transferase Mu 3, alpha-1-acid glycoprotein 2, serum amyloid P-component, aminopeptidase N, neprilysin, FAS, and miR-10b-3p, miR-122-5p, miR-205-5p, miR-222-3p, miR-34c-5p, miR-509-3-5p, miR-888-5p, miR-892a, miR-363-3p, miR-941, miR-146a-5p, miR-744-5p. These molecules have low IIV and may be promising candidate biomarkers of male fertility and reproductive health.

Epigenetic transgenerational inheritance of toxicant exposure-specific non-coding RNA in sperm.

Environmentally induced epigenetic transgenerational inheritance of phenotypic variation and disease susceptibility requires the germ cell (sperm or egg) transmission of integrated epigenetic mechanisms involving DNA methylation, histone modifications, and non-coding RNA (ncRNA) actions. Previous studies have demonstrated that transgenerational exposure and disease-specific differential DNA methylation regions (DMRs) in sperm are observed and that ncRNA-mediated DNA methylation occurs. The current study was designed to determine if transgenerational exposure-specific ncRNAs exist in sperm. Specifically, toxicants with distinct mechanisms of action including the fungicide vinclozolin (anti-androgenic), pesticide dichlorodiphenyltrichloroethane (estrogenic), herbicide atrazine (endocrine disruptor at cyclic adenosine monophosphate level), and hydrocarbon mixture jet fuel (JP8) (aryl hydrocarbon receptor disruptor) were used to promote transgenerational disease phenotypes in F3 generation outbred rats. New aliquots of sperm, previously collected and used for DNA methylation analyses, were used in the current study for ncRNA sequencing analyses of nuclear RNA. Significant changes in transgenerational sperm ncRNA were observed for each transgenerational exposure lineage. The majority of ncRNA was small noncoding RNAs including piwi-interacting RNA, tRNA-derived small RNAs, microRNAs, rRNA-derived small RNA, as well as long ncRNAs. Although there was some overlap among the different classes of ncRNA across the different exposures, the majority of differentially expressed ncRNAs were exposure-specific with no overlapping ncRNA between the four different exposure lineages in the transgenerational F3 generation sperm nuclear ncRNAs. The ncRNA chromosomal locations and gene associations were identified for a small number of differential expressed ncRNA. Interestingly, an overlap analysis between the transgenerational sperm DMRs and ncRNA chromosomal locations demonstrated small populations of overlapping ncRNA, but a large population of non-overlapping ncRNAs. Observations suggest that transgenerational sperm ncRNAs have both exposure-specific populations within the different classes of ncRNA, as well as some common populations of ncRNAs among the different exposures. The lack of co-localization of many of the ncRNAs with previously identified transgenerational DMRs suggests a distal integration of the different epigenetic mechanisms. The potential use of ncRNA analyses for transgenerational toxicant exposure assessment appears feasible.

MRDPDA: A multi-Laplacian regularized deepFM model for predicting piRNA-disease associations.

PIWI-interacting RNAs (piRNAs) are a typical class of small non-coding RNAs, which are essential for gene regulation, genome stability and so on. Accumulating studies have revealed that piRNAs have significant potential as biomarkers and therapeutic targets for a variety of diseases. However current computational methods face the challenge in effectively capturing piRNA-disease associations (PDAs) from limited data. In this study, we propose a novel method, MRDPDA, for predicting PDAs based on limited data from multiple sources. Specifically, MRDPDA integrates a deep factorization machine (deepFM) model with regularizations derived from multiple yet limited datasets, utilizing separate Laplacians instead of a simple average similarity network. Moreover, a unified objective function to combine embedding loss about similarities is proposed to ensure that the embedding is suitable for the prediction task. In addition, a balanced benchmark dataset based on piRPheno is constructed and a deep autoencoder is applied for creating reliable negative set from the unlabeled dataset. Compared with three latest methods, MRDPDA achieves the best performance on the pirpheno dataset in terms of the five-fold cross validation test and independent test set, and case studies further demonstrate the effectiveness of MRDPDA.

FlaHMM: unistrand flamenco-like piRNA cluster prediction in Drosophila species using hidden Markov models.

PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs that are essential for transposon control in animal gonads. In Drosophila ovarian somatic cells, piRNAs are transcribed from large genomic regions called piRNA clusters, which are enriched for transposon fragments and act as a memory of past invasions. Despite being widely present across Drosophila species, somatic piRNA clusters are difficult to identify and study due to their lack of sequence conservation and limited synteny. Current identification methods rely on either extensive manual curation or availability of high-throughput small RNA sequencing data, limiting large-scale comparative studies. We now present FlaHMM, a hidden Markov model developed to automate genomic annotation of flamenco-like unistrand piRNA clusters in Drosophila species, requiring only a genome assembly and transposon annotations. FlaHMM uses transposable element content across 5- or 10-kb bins, which can be calculated from genome sequence alone, and is thus able to detect candidate piRNA clusters without the need to obtain flies and experimentally perform small RNA sequencing. We show that FlaHMM performs on par with piRNA-guided or manual methods, and thus provides a scalable and efficient approach to piRNA cluster annotation in new genome assemblies. FlaHMM is freely available at https://github.com/Hannon-lab/FlaHMM under an MIT licence.

PiRNA PROPER Suppresses DUSP1 Translation by Targeting N6-Methyladenosine-Mediated RNA Circularization to Promote Oncogenesis of Prostate Cancer.

Genetic and epigenetic alterations occur in many physiological and pathological processes. The existing knowledge regarding the association of PIWI-interacting RNAs (piRNAs) and their genetic variants on risk and progression of prostate cancer (PCa) is limited. In this study, three genome-wide association study datasets are combined, including 85,707 PCa cases and 166,247 controls, to uncover genetic variants in piRNAs. Functional investigations involved manipulating piRNA expression in cellular and mouse models to study its oncogenetic role in PCa. A specific genetic variant, rs17201241 is identified, associated with increased expression of PROPER (piRNA overexpressed in prostate cancer) in tumors and are located within the gene, conferring an increased risk and malignant progression of PCa. Mechanistically, PROPER coupled with YTHDF2 to recognize N6-methyladenosine (m6A) and facilitated RNA-binding protein interactions between EIF2S3 at 5'-untranslated region (UTR) and YTHDF2/YBX3 at 3'-UTR to promote DUSP1 circularization. This m6A-dependent mRNA-looping pattern enhanced DUSP1 degradation and inhibited DUSP1 translation, ultimately reducing DUSP1 expression and promoting PCa metastasis via the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Inhibition of PROPER expression using antagoPROPER effectively suppressed xenograft growth, suggesting its potential as a therapeutic target. Thus, targeting piRNA PROPER-mediated genetic and epigenetic fine control is a promising strategy for the concurrent prevention and treatment of PCa.

LKLPDA: A Low-Rank Fast Kernel Learning Approach for Predicting piRNA-Disease Associations.

Piwi-interacting RNAs (piRNAs) are increasingly recognized as potential biomarkers for various diseases. Investig-ating the complex relationship between piRNAs and diseases through computational methods can reduce the costs and risks associated with biological experiments. Fast kernel learning (FKL) is a classical method for multi-source data fusion that is widely employed in association prediction research. However, biological networks are noisy due to the limitations of measurement technology and inherent natural variation, which can hamper the effectiveness of the network-based ideal kernel. The conventional FKL method does not address this issue. In this study, we propose a low-rank fast kernel learning (LRFKL) algorithm, which consists of low-rank representation (LRR) and the FKL algorithm. The LRFKL algorithm is designed to mitigate the effects of noise on the network-based ideal kernel. Using LRFKL, we propose a novel approach for predicting piRNA-disease associations called LKLPDA. Specifically, we first compute the similarity matrices for piRNAs and diseases. Then we use the LRFKL to fuse the similarity matrices for piRNAs and diseases separately. Finally, the LKLPDA employs AutoGluon-Tabular for predictive analysis. Computational results show that LKLPDA effectively predicts piRNA-disease associations with higher accuracy compared to previous methods. In addition, case studies confirm the reliability of the model in predicting piRNA-disease associations. Availability and implementation: The LKLPDA software and data are freely available at https://github.com/Shiqzz/LKLPDA-master.git.

FBXO24 deletion causes abnormal accumulation of membraneless electron-dense granules in sperm flagella and male infertility

Ribonucleoprotein (RNP) granules are membraneless electron-dense structures rich in RNAs and proteins, and involved in various cellular processes. Two RNP granules in male germ cells, intermitochondrial cement and the chromatoid body (CB), are associated with PIWI-interacting RNAs (piRNAs) and are required for transposon silencing and spermatogenesis. Other RNP granules in male germ cells, the reticulated body and CB remnants, are also essential for spermiogenesis. In this study, we disrupted FBXO24, a testis-enriched F-box protein, in mice and found numerous membraneless electron-dense granules accumulated in sperm flagella. Fbxo24 knockout (KO) mice exhibited malformed flagellar structures, impaired sperm motility, and male infertility, likely due to the accumulation of abnormal granules. The amount and localization of known RNP granule-related proteins were not disrupted in Fbxo24 KO mice, suggesting that the accumulated granules were distinct from known RNP granules. Further studies revealed that RNAs and two importins, IPO5 and KPNB1, abnormally accumulated in Fbxo24 KO spermatozoa and that FBXO24 could ubiquitinate IPO5. In addition, IPO5 and KPNB1 were recruited to stress granules, RNP complexes, when cells were treated with oxidative stress or a proteasome inhibitor. These results suggest that FBXO24 is involved in the degradation of IPO5, disruption of which may lead to the accumulation of abnormal RNP granules in sperm flagella.

FBXO24 deletion causes abnormal accumulation of membraneless electron-dense granules in sperm flagella and male infertility.

Ribonucleoprotein (RNP) granules are membraneless electron-dense structures rich in RNAs and proteins, and involved in various cellular processes. Two RNP granules in male germ cells, intermitochondrial cement and the chromatoid body (CB), are associated with PIWI-interacting RNAs (piRNAs) and are required for transposon silencing and spermatogenesis. Other RNP granules in male germ cells, the reticulated body and CB remnants, are also essential for spermiogenesis. In this study, we disrupted FBXO24, a testis-enriched F-box protein, in mice and found numerous membraneless electron-dense granules accumulated in sperm flagella. Fbxo24 knockout (KO) mice exhibited malformed flagellar structures, impaired sperm motility, and male infertility, likely due to the accumulation of abnormal granules. The amount and localization of known RNP granule-related proteins were not disrupted in Fbxo24 KO mice, suggesting that the accumulated granules were distinct from known RNP granules. Further studies revealed that RNAs and two importins, IPO5 and KPNB1, abnormally accumulated in Fbxo24 KO spermatozoa and that FBXO24 could ubiquitinate IPO5. In addition, IPO5 and KPNB1 were recruited to stress granules, RNP complexes, when cells were treated with oxidative stress or a proteasome inhibitor. These results suggest that FBXO24 is involved in the degradation of IPO5, disruption of which may lead to the accumulation of abnormal RNP granules in sperm flagella.

The genomes of all lungfish inform on genome expansion and tetrapod evolution.

The genomes of living lungfishes can inform on the molecular-developmental basis of the Devonian sarcopterygian fish-tetrapod transition. We de novo sequenced the genomes of the African (Protopterus annectens) and South American lungfishes (Lepidosiren paradoxa). The Lepidosiren genome (about 91 Gb, roughly 30 times the human genome) is the largest animal genome sequenced so far and more than twice the size of the Australian (Neoceratodus forsteri)1 and African2 lungfishes owing to enlarged intergenic regions and introns with high repeat content (about 90%). All lungfish genomes continue to expand as some transposable elements (TEs) are still active today. In particular, Lepidosiren's genome grew extremely fast during the past 100 million years (Myr), adding the equivalent of one human genome every 10 Myr. This massive genome expansion seems to be related to a reduction of PIWI-interacting RNAs and C2H2 zinc-finger and Krüppel-associated box (KRAB)-domain protein genes that suppress TE expansions. Although TE abundance facilitates chromosomal rearrangements, lungfish chromosomes still conservatively reflect the ur-tetrapod karyotype. Neoceratodus' limb-like fins still resemble those of their extinct relatives and remained phenotypically static for about 100 Myr. We show that the secondary loss of limb-like appendages in the Lepidosiren-Protopterus ancestor was probably due to loss of sonic hedgehog limb-specific enhancers.

PiR-823 tale as emerging cancer-hallmark molecular marker in different cancer types: a step-toward ncRNA-precision.

PIWI-interacting RNAs (piRNAs) have received a lot of attention for their functions in cancer research. This class of short non-coding RNAs (ncRNA) has roles in genomic stability, chromatin remodeling, messenger RNA (mRNA) integrity, and genome structure. We summarized the mechanisms underlying the biogenesis and regulatory molecular functions of piRNAs. Among all piRNAs studied in cancer, this review offers a comprehensive analysis of the emerging roles of piR-823 in various types of cancer, including colorectal, gastric, liver, breast, and renal cancers, as well as multiple myeloma. piR-823 has emerged as a crucial modulator of various cancer hallmarks through regulating multiple pathways. In the current review, we analyzed several databases and conducted an extensive literature search to explore the influence of piR-823 in carcinogenesis in addition to describing the potential application of piR-823 as prognostic and diagnostic markers as well as the therapeutic potential toward ncRNA precision.

PiR112710 attenuates diabetic cardiomyopathy through inhibiting Txnip/NLRP3-mediated pyroptosis in db/db mice

PIWI-interacting RNAs (piRNAs) are involved in the regulation of hypertrophic cardiomyopathy, heart failure and myocardial methylation. However, their functions and the underlying molecular mechanisms in diabetic cardiomyopathy (DCM) have yet to be fully elucidated. In the present study, a pyroptosis-associated piRNA (piR112710) was identified that ameliorates cardiac remodeling through targeting the activation of inflammasomes and mitochondrial dysfunction that are mediated via the thioredoxin-interacting protein (Txnip)/NLRP3 signaling axis. Subsequently, the cardioprotective effects of piR112710 on both the myocardium from db/db mice and cardiomyocytes from neonatal mice that were incubated with a high concentration of glucose combined with palmitate were examined. piR112710 was found to significantly improve cardiac dysfunction in db/db mice, characterized by improved echocardiography, lower levels of fibrosis, attenuated expression levels of inflammatory factors and pyroptosis-associated proteins (namely, Txnip, ASC, NLRP3, caspase-1 and GSDMD-N), and enhanced myocardial mitochondrial respiratory functions. In cultured neonatal mice cardiomyocytes, piR112710 deficiency and high glucose along with palmitate treatment led to significantly upregulated expression levels of pyroptosis associated proteins and collagens, oxidative stress, mitochondrial dysfunction and increased levels of inflammatory factors. Supplementation with piR112710, however, led to a reversal of the aforementioned changes induced by high glucose and palmitate. Mechanistically, the cardioprotective effect of piR112710 appears to be dependent upon effective elimination of reactive oxygen species and inactivation of the Txnip/NLRP3 signaling axis. Taken together, the findings of the present study have revealed that the piRNA-mediated inhibitory mechanism involving the Txnip/NLRP3 axis may participate in the regulation of pyroptosis, which protects against DCM both in vivo and in vitro. piR112710 may therefore be a potential therapeutic target for the reduction of myocardial injury caused by cardiomyocyte pyroptosis in DCM.

Oral Piwi-Interacting RNA Delivery Mediated by Green Tea-Derived Exosome-Like Nanovesicles for the Treatment of Aortic Dissection.

Aortic dissection (AD) is a severe cardiovascular disease necessitating active therapeutic strategies for early intervention and prevention. Nucleic acid drugs, known for their potent molecule-targeting therapeutic properties, offer potential for genetic suppression of AD. Piwi-interacting RNAs, a class of small RNAs, hold promise for managing cardiovascular diseases. Limited research on these RNAs and AD exists. This study demonstrates that an antagomir targeting heart-apoptosis-associated piRNA (HAAPIR) effectively regulates vascular remodeling, mitigating AD occurrence and progression through the myocyte enhancer factor 2D (Mef2D) and matrix metallopeptidase 9 (MMP9) pathways. Green tea-derived plant exosome-like nanovesicles (PELNs) are used for oral administration of antagomir. The antagomir-HAAPIR-nanovesicle complex, after purification and optimization, exhibits a high packing rate, while the antagomir is resistant to enzyme digestion. Administered to mice, the complex targets the aortic lesion, reducing AD incidence and improving survival. Moreover, MMP9 and Mef2D expression decrease significantly, inhibiting the phenotypic conversion of human aortic smooth muscle cells. PELNs encapsulate the antagomir-HAAPIR complex, maintaining stability, mediating transport into the bloodstream, and delivering Piwi-interacting RNAs to AD sites. Thus, HAAPIR is a potential target for persistent clinical AD prevention and treatment, and nanovesicle-encapsulated nucleic acids offer a promising cardiovascular disease treatment, providing insights for other therapeutic targets.

Identification of piRNA Expression Profiles in Vitiligo

Objective: Vitiligo is a systemic dermatological disorder characterized by skin depigmentation due to melanocyte damage and dysfunction. The treatment of vitiligo remains a challenging aspect in dermatological practice. PIWI-interacting RNAs (piRNAs), approximately 24–32 nucleotides in length, are crucial in the epigenetic regulation of developmental processes. However, research on piRNA expression profiling in vitiligo is limited. This study aimed to identify and characterize piRNAs in skin tissues from vitiligo patients and healthy controls. Methods: We compared and analyzed piRNA expression profiles of human vitiligo skin by RNA sequencing. Results and Discussion: Our findings revealed a pronounced preference for uridine (U) at the 5′ end of piRNAs, predominantly originating from repeat and other genomic regions. Notably, we detected 73 differentially expressed piRNAs between the patient and control groups, with 40 piRNAs upregulated and 33 downregulated in vitiligo patients. Bioinformatics analysis indicated that the genes responsible for piRNA production were more prevalent in metabolic processes and implicated in regulating the PI3K-Akt and AMPK signaling pathways. Conclusions: The elucidation of piRNA expression profiles enhances our understanding of their functional roles in the pathogenesis of vitiligo.

New insights into the function and mechanisms of piRNA PMLCPIR in promoting PM2.5-induced lung cancer

IntroductionExtensive studies have established the correlation between long-term PM2.5 exposure and lung cancer, yet the mechanisms underlying this association remain poorly understood. PIWI-interacting RNAs (piRNAs), a novel category of small non-coding RNAs, serve important roles in various diseases. However, their biological function and mechanism in PM2.5-induced lung cancer have not been thoroughly investigated. ObjectivesWe aimed to explore the oncogenic role of piRNA in lung cancer induced by PM2.5 exposure, as well as the underlying mechanisms. MethodsWe conducted a PM2.5-induced human lung epithelial cell malignant transformation model. Human samples were used to further verify the finding. In vitro proliferation, migration, and invasion assays were performed to study the function of piRNA. RNA-sequencing was used to elucidate the the mechanisms of how piRNA mediates cell functions. PiRNA pull-down and computational docking analysis were conducted to identify proteins that binding to piRNA. In vivo experiments were used to explore whether inhibition of PMLCPIR could have a therapeutic effect on lung cancer. ResultsWe identified a new up-regulated piRNA, termed PM2.5-induced lung cancer up-regulation piRNA (PMLCPIR), which promotes the proliferation of PM2.5-transformed cells and lung cancer cells. RNA sequencing revealed ITGB1 as a downstream target of PMLCPIR. Importantly, PMLCPIR binds to nucleolin (NCL) and increases the expression of its target gene, ITGB1, thereby activating PI3K/AKT signaling. The inhibition of PMLCPIR could promote apoptosis in lung cancer cells and enhance their chemosensitivity to anti-tumor drugs. ConclusionWe systematically identified the alterations of piRNA expression profiles in the PM2.5-induced malignant transformation model. Then, PMLCPIR was recognized as a novel oncogenic piRNA in PM2.5-induced lung cancer. Mechanically, PMLCPIR binds to NCL, enhancing ITGB1 expression and activating the ontogenetic PI3K/AKT signaling, potentially contributing to lung cancer progression. This study provides novel insights into the revelation of a new epigenetic regulator in PM2.5-induced lung cancer.

PiR-27222 mediates PM2.5-induced lung cancer by resisting cell PANoptosis through the WTAP/m6A axis

PM2.5 pollution has been associated with the incidence of lung cancer, but the underlying mechanism is still unclear. PIWI-interacting RNAs (piRNAs), initially identified in germline cells, have emerged as a novel class of small non-coding RNAs (26 – 32 nucleotides) with diverse functions in various diseases, including cancer. However, the role and mechanism of piRNAs in the development of PM2.5-induced lung cancer remain to be clarified. In the presented study, we used a PM2.5-induced malignant transformation cell model to analyze the change of piRNA profiles. Among the disturbed piRNAs, piR-27222 was identified as an oncogene that inhibited cell death in a m6A-dependent manner. Mechanistically, we found that piR-27222 could deubiquitinate and stabilize eIF4B by directly binding to eIF4B and reducing its interaction with PARK2. The enhanced expression of eIF4B, in turn, promoted the expression of WTAP, leading to increased m6A modification in the Casp8 transcript. Consequently, the stability of Casp8 transcripts was reduced, rendering lung cancer cells resistant to PANoptosis. Collectively, our findings reveal that PM2.5 exposure up-regulated piR-27222 expression, which could affect EIF4B/WTAP/m6A axis, thereby inhibiting PANoptosis of cells and promoting lung cancer. Our study provides new insights into understanding the epigenetic mechanisms underlining PM2.5-induced lung cancer.

Recent advances of PIWI-interacting RNA in cardiovascular diseases.

The relationship between noncoding RNAs (ncRNAs) and human diseases has been a hot topic of research, but the study of ncRNAs in cardiovascular diseases (CVDs) is still in its infancy. PIWI-interacting RNA (piRNA), a small ncRNA that binds to the PIWI protein to maintain genome stability by silencing transposons, was widely studied in germ lines and stem cells. In recent years, piRNA has been shown to be involved in key events of multiple CVDs through various epigenetic modifications, revealing the potential value of piRNA as a new biomarker or therapeutic target. This review explores origin, degradation, function, mechanism and important role of piRNA in CVDs, and the promising therapeutic targets of piRNA were summarized. This review provide a new strategy for the treatment of CVDs and lay a theoretical foundation for future research. piRNA can be used as a potential therapeutic target and biomaker in CVDs. piRNA influences apoptosis, inflammation and angiogenesis by regulating epigenetic modificaions. Critical knowledge gaps remain in the unifying piRNA nomenclature and PIWI-independent function.

Characterization of piRNAs in Diploid and Triploid Pacific Oyster Gonads: Exploring Their Potential Roles in Triploid Sterility.

PIWI-interacting RNAs (piRNAs) are crucial for silencing transposable elements, germ cell development, and gametogenesis. Triploid Pacific oysters (Crassostrea gigas) are vital in the oyster aquaculture industry due to reduced fertility and rapid growth. This study integrates piRNA and mRNA expression analyses to elucidate their potential contributions to the sterility of triploid C. gigas. Bioinformatics analysis reveals a distinct U-bias at the 5' terminal of oyster piRNAs. The abundance of piRNA clusters is reduced in triploid gonads compared to diploid gonads, particularly in sterile gonads, with a significant decrease in piRNA numbers. A specific piRNA cluster is annotated with the PPP4R1 gene, which is downregulated in infertile female triploids and exhibits a negative correlation with three piRNAs within the cluster. Differential expression analysis identified 46 and 88 piRNAs in female and male comparison groups, respectively. In female sterile triploids, the expression of three target genes of differentially expressed piRNAs associated with cell division showed downregulation, suggesting the potential roles of piRNAs in the regulation of cell division-related genes, contributing to the gonad arrest observed in female triploid oysters. In male triploid oysters, piRNAs potentially interact with the target genes associated with spermatogenesis, including TSSK4, SPAG17, and CCDC81. This study provides a concise overview of piRNAs expression in oyster gonads, offering insights into the regulatory role of piRNAs in triploid sterility.

Deformed wing virus genotypes A and B do not elicit immunologically different responses in naïve honey bee hosts.

Iflavirus aladeformis (Picornavirales: Iflaviridae), commonly known as deformed wing virus(DWV), in association with Varroa destructor Anderson and Trueman (Mesostigmata: Varroidae), is a leading factor associated with honey bee (Apis mellifera L. [Hymenoptera: Apidae]) deaths. The virus and mite have a near global distribution, making it difficult to separate the effect of one from the other. The prevalence of two main DWV genotypes (DWV-A and DWV-B) has changed over time, leading to the possibility that the two strains elicit a different immune response by the host. Here, we use a honey bee population naïve to both the mite and the virus to investigate if honey bees show a different immunological response to DWV genotypes. We examined the expression of 19 immune genes by reverse transcription quantitative PCR (RT-qPCR) and analysed small RNA after experimental injection with DWV-A and DWV-B. We found no evidence that DWV-A and DWV-B elicit different immune responses in honey bees. RNA interference genes were up-regulated during DWV infection, and small interfering RNA (siRNA) responses were proportional to viral loads yet did not inhibit DWV accumulation. The siRNA response towards DWV was weaker than the response to another honey bee pathogen, Triatovirus nigereginacellulae (Picornavirales: Dicistroviridae; black queen cell virus), suggesting that DWV is comparatively better at evading host antiviral defences. There was no evidence for the production of virus-derived Piwi-interacting RNAs (piRNAs) in response to DWV. In contrast to previous studies, and in the absence of V. destructor, we found no evidence that DWV has an immunosuppressive effect. Overall, our results advance our understanding of the immunological effect that DWV in isolation elicits in honey bees.

Enigmatic Pachytene PIWI-Interacting RNAs.

PIWI-interacting RNAs (piRNAs), a class of small RNAs, are renowned for their roles in sequencing-dependent targeting and suppressing transposable elements (TEs). Nevertheless, a majority of mammalian piRNAs, expressing at pachytene stage of meiosis, known as pachytene piRNAs, are devoid of discernible targets, casting a veil of enigma over their functional significance. Overturning the notion that this unusual class of piRNAs functions beyond TE silencing, we recently demonstrated that pachytene piRNAs play an essential and conserved role in silencing young and actively transposing TEs across amniotes. However, only 1% of pachytene piRNAs target active TEs. The biological significance of the abundant non-TE piRNAs, coproduced from the same precursors as TE piRNAs, remains unclear. Here, we provide a comprehensive summary of the potential roles of non-TE piRNAs, and thus propose that these non-TE piRNAs either bolster the action of TE piRNAs or provide the host genome a preexisting mechanism to suppress the potential invasion of novel TEs in the future.