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Two non-covalently linked copies of the retrovirus genome are specifically recruited to the site of virus particle assembly and packaged into released particles. Retroviral RNA packaging requires RNA export of the unspliced genomic RNA from the nucleus, translocation of the genome to virus assembly sites, and specific interaction with Gag, the main viral structural protein. While some aspects of the RNA packaging process are understood, many others remain poorly understood. In this review, we provide an update on recent advancements in understanding the mechanism of RNA packaging for retroviruses that cause disease in humans, i.e., HIV-1, HIV-2, and HTLV-1, as well as advances in the understanding of the details of genomic RNA nuclear export, genome translocation to virus assembly sites, and genomic RNA dimerization.

Colorectal cancer (CRC) is associated with high morbidity rates. Long non-coding RNAs (lncRNAs) participate in the development of CRC. However, the potential roles of lncRNA plasmacytoma variant translocation 1 (PVT1) in CRC remain unknown. Therefore, the aim of the present study was to investigate the potential roles of PVT1 in CRC. Reverse transcription-quantitative PCR and western blot analyses were conducted to determine the mRNA and protein expression levels. The cellular behaviors were detected using 5-Ethynyl-2′-deoxyuridine, Cell Counting Kit-8 and flow cytometry assays. The interaction between PVT1 and microRNA (miR)-761 or MAPK1 was confirmed using a dual-luciferase reporter assay. Moreover, the Pearson's method was applied for correlation analysis. The results demonstrated that the expression levels of PVT1 and MAPK1 were upregulated, while miR-761 was downregulated in CRC tissues. The expression of PVT1 was positively correlated with MAPK1 and negatively correlated with miR-761. In addition, PVT1 sponged miR-761 to upregulate MAPK1 expression. It was found that the knockdown of PVT1 expression inhibited the proliferation and promoted the apoptosis of CRC cells, which was more potent in cells transfected with miR-761. The regulatory role of small interfering RNA-PVT1 on the expression of apoptosis-related genes was reduced by MAPK1. Collectively, the present results suggested that knockdown of PVT1 may inhibit the progression of CRC by regulating the miR-761/MAPK1 axis, which may provide a promising biomarker for the treatment of CRC.

Background Long non‐coding RNA plasmacytoma variant translocation 1 (lnc‐PVT1) exacerbates inflammation and induces T helper (Th) 1/Th2 imbalance in allergic diseases, but its clinical role in allergic rhinitis (AR) remains unclear. Hence, we conducted this study to compare lnc‐PVT1 expression among AR children, disease controls (DCs), and health controls (HCs), aiming to investigate its clinical application in AR children. Methods Sixty AR children, 30 DCs, and 30 HCs were enrolled in the study, and then, their lnc‐PVT1 expression in peripheral blood mononuclear cell was detected. Serum interferon‐gamma (IFN‐γ), interleukin 10 (IL‐10), Th1, and Th2 cells in AR children were also analyzed. Besides, lnc‐PVT1 was also detected at Week (W)4 after treatment in AR patients. Results Lnc‐PVT1 was upregulated in AR children compared with DCs and HCs (both p < 0.001). Lnc‐PVT1 was positively related to nasal rhinorrhea score, itching score, congestion score, and total nasal symptom score (TNSS) in AR children (all p < 0.050), instead of sneezing score (p = 0.115). Lnc‐PVT1 negatively associated with Th1 cells in AR children (p = 0.028) also exhibited a negative correlation trend with IFN‐γ (but without statistical significance) (p = 0.065). Differently, lnc‐PVT1 was positively related to Th2 cells (p = 0.012) and IL‐10 (p = 0.021) in AR children. Besides, lnc‐PVT1 and TNSS were reduced at W4 after treatment in AR children (both p < 0.001); notably, lnc‐PVT1 expression decline was correlated with TNSS decline during treatment (p = 0.013). Conclusion Lnc‐PVT1 works as a biomarker, whose aberrant expression is related to disease severity, Th1/Th2 imbalance, and its decrement can reflect treatment outcome in AR children. The current study enrolled 60 AR children, 30 DCs, and 30 HCs and then detected their lnc‐PVT1 in PBMC. For AR children only, serum IFN‐γ, IL‐10, Th1, and Th2 cells at W0 and lnc‐PVT1 in PBMC at W4 were also analyzed. Interestingly, lnc‐PVT1 was upregulated in AR children compared with DCs and HCs. Lnc‐PVT1 was positively related to nasal rhinorrhea score, itching score, congestion score, and TNSS in AR children. Moreover, lnc‐PVT1 was negatively associated with Th1 cells in AR children and also exhibited a negative correlation trend with IFN‐γ (but without statistical significance). Differently, lnc‐PVT1 was positively related to Th2 cells and IL‐10 in AR children. Besides, lnc‐PVT1 and TNSS were reduced at W4 after treatment in AR children; notably, lnc‐PVT1 decline was correlated with TNSS decline during treatment.

Nanopore-based DNA analysis is a new single-molecule technique that involves monitoring the flow of ions through a narrow pore, and detecting changes in this flow as DNA molecules also pass through the pore. It has the potential to carry out a range of laboratory and medical DNA analyses, orders of magnitude faster than current methods. Initial experiments used a protein channel for its pre-defined, precise structure, but since then several approaches for the fabrication of solid-state pores have been developed. These aim to match the capabilities of biochannels, while also providing increased durability, control over pore geometry and compatibility with semiconductor and microfluidics fabrication techniques. This review summarizes each solid-state nanopore fabrication technique reported to date, and compares their advantages and disadvantages. Methods and applications for nanopore surface modification are also presented, followed by a discussion of approaches used to measure pore size, geometry and surface properties. The review concludes with an outlook on the future of solid-state nanopores.

Telomerase synthesizes telomeres at the ends of linear chromosomes by repeated reverse transcription from a short RNA template. Crystal structures of Tribolium castaneum telomerase reverse transcriptase (tcTERT) and cryoelectron microscopy (cryo-EM) structures of human and Tetrahymena telomerase have revealed conserved features in the reverse-transcriptase domain, including a cavity near the DNA 3′ end and snug interactions with the RNA template. For the RNA template to translocate, it needs to be unpaired and separated from the DNA product. Here we investigate the potential of the structural cavity to accommodate a looped-out DNA bulge and enable the separation of the RNA/DNA hybrid. Using tcTERT as a model system, we show that a looped-out telomeric repeat in the DNA primer can be accommodated and extended by tcTERT but not by retroviral reverse transcriptase. Mutations that reduce the cavity size reduce the ability of tcTERT to extend the looped-out DNA substrate. In agreement with cryo-EM structures of telomerases, we find that tcTERT requires a minimum of 4 bp between the RNA template and DNA primer for efficient DNA synthesis. We also have determined the ternary-complex structure of tcTERT including a downstream RNA/DNA hybrid at 2.0-Å resolution and shown that a downstream RNA duplex, equivalent to the 5′ template-boundary element in telomerase RNA, enhances the efficiency of telomere synthesis by tcTERT. Although TERT has a preformed active site without the open-and-closed conformational changes, it contains cavities to accommodate looped-out RNA and DNA. The flexible RNA–DNA binding likely underlies the processivity of telomeric repeat addition.

Nanopore-based DNA analysis is a single-molecule technique with revolutionary potential. It promises to carry out a range of analyses, orders of magnitude faster than current methods, including length measurement, specific sequence detection, single-molecule dynamics and even sequencing. The concept involves using an applied voltage to drive DNA molecules through a narrow pore that separates chambers of electrolyte solution. This voltage also drives a flow of electrolyte ions through the pore, measured as an electric current. When molecules pass through the pore, they block the flow of ions and, thus, their structure and length can be determined based on the degree and duration of the resulting current reductions. In this review, I explain the nanopore-based DNA analysis concept and briefly explore its historical foundations, before discussing and summarizing all experimental results reported to date. I conclude with a summary of the obstacles that must be overcome for it to realize its promised potential.

To investigate how lncRNA plasmacytoma variant translocation 1 (PVT1) contributed to the pathogenesis of gallbladder adenocarcinoma (GBA). Bioinformatics techniques were used to analyze differentially expressed lncRNA, and downstream miRNA and mRNA were identified using databases. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting were utilized to analyze the RNA and protein expressions in different cells. The binding relationships between different genes were confirmed utilizing luciferase assay and RNA Immunoprecipitation (RIP) assay. Cell growth and migration were examined through CCK-8, colony formation, and Transwell assays. Several in vivo experiments were utilized to determine how the PVT1/miR-2355-5p/AGO1 pathway on tumor growth. Elevated PVT1 was observed in GBA cells, which may further aggravate cell malignant properties. Based on bioinformatics analysis, an interaction between miR-2355-5p and either PVT1 or AGO1 was identified, which was confirmed utilizing dual luciferase reporter assays and RIP assays. Silencing PVT1 (si-PVT1) led to a reduction in AGO1 expression, while depletion of miR-2355-5p reversed this effect. In vivo, PVT1 knockdown significantly inhibited tumor growth, an effect that was reversed by miR-2355-5p downregulation. This study showed that PVT1 facilitated GBA progression via the modulation of the miR-2355-5p/AGO1 axis. These findings underscored the potential therapeutic significance of targeting the lncRNA PVT1 in the treatment of GBA.

Objectives Studies have widely explored in the filed of ischemic stroke (IS) with their focus on transcription factors. However, few studies have pivoted on sex determining region Y-box 2 (SOX2) in IS. Thus, this study is launched to figure out the mechanisms of SOX2 in IS. Methods Rat middle cerebral artery occlusion (MCAO) was established as a stroke model. MCAO rats were injected with depleted SOX2 or long non-coding RNA plasmacytoma variant translocation 1 (PVT1) to explore their roles in neurological deficits, cerebral water content, neuron survival, apoptosis and oxidative stress. The relationship among SOX2, PVT1, microRNA (miR)-24-3p and signal transducer and activator of transcription 3 (STAT3) was verified by a series of experiments. Results SOX2, PVT1 and STAT3 were highly expressed while miR-24-3p was poorly expressed in cerebral cortex tissues of MCAO rats. Depleted SOX2 or PVT1 alleviated brain injury in MCAO rats as reflected by neuronal apoptosis and oxidative stress restriction, brain water content reduction, and neurological deficit and neuron survival improvements. Overexpression of PVT1 functioned oppositely. Restored miR-24-3p abolished PVT1 overexpression-induced brain injury in MCAO rats. SOX2 directly promoted PVT1 expression and further increased STAT3 by sponging miR-24-3p. Conclusion This study presents that depleting SOX2 improves IS via PVT1/miR-24-3p/STAT3 axis which may broaden our knowledge about the mechanisms of SOX2/PVT1/miR-24-3p/STAT3 axis and provide a reference of therapy for IS.

Long noncoding RNAs (lncRNAs) and microRNAs (miRs) serve critical roles in various cellular processes and can be used as noninvasive biomarkers in human diseases. The present study aimed to investigate the effects of lncRNA plasmacytoma variant translocation 1 (PVT1) and miR-190a-5p on vascular endothelial cell (EC) proliferation and assess their clinical value in the diagnosis of chronic heart failure (CHF). The expression of PVT1 and miR-190a-5p was investigated using reverse transcription-quantitative PCR. The interaction between PVT1 and miR-190a-5p was confirmed using a luciferase reporter assay. A Cell Counting Kit-8 assay was performed to examine EC proliferation. A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of PVT1 and miR-190a-5p. PVT1 directly decreased the expression of miR-190a-5p in ECs. Overexpression of miR-190a-5p in ECs led to inhibited cell proliferation and miR-190a-5p antagonized the promotive effect of PVT1 on EC proliferation. Serum expression of PVT1 increased, while serum expression of miR-190a-5p decreased in patients with CHF compared with healthy controls (all P<0.001). The ROC curves indicated that PVT1 and miR-190a-5p were two diagnostic biomarkers of CHF, and the combination of PVT1 and miR-190a-5p showed better diagnostic accuracy compared with using PVT1 or miR-190-5p alone. In conclusion, the present study demonstrated that PVT1 promoted EC proliferation by directly suppressing miR-190a-5p. Circulating PVT1 and miR-190a-5p are possible two candidate diagnostic biomarkers of CHF, and the combined detection of the two indicators may provide a novel approach for CHF diagnosis.

Background As a type of chronic autoimmune joint disease, rheumatoid arthritis (RA) is a disorder, characterized by a variety of physical symptoms as well as RA fibroblast-like synoviocyte (RA-FLS) proliferation. More recently, long non-coding RNAs (lncRNAs) have been implicated in the progression of various diseases including the progression of RA. Hence, the aim of the current study was to investigate the role by which the lncRNA, plasmacytoma variant translocation 1 (PVT1), influences RA-FLSs and its ability to modulate the methylation of sirtuin 6 (sirt6) . Methods RA rat models were initially established to determine the expression of PVT1 and sirt6 in synovial tissues and RA-FLSs. Elevation or depletion of PVT1 or sirt6 was achieved by means of transformation with plasmids in order to investigate their effects on RA-FLS proliferation, inflammation and apoptosis. The localization of PVT1 and its binding ability to the sirt6 promoter region were also explored in an attempt to elucidate the correlation between PVT1 and sirt6 methylation. Results High expression of PVT1 and low expression of sirt6 were detected in the synovial tissues and RA-FLSs of the rat models. RA-FLSs treated with sh-PVT1 or oe-sirt6 exhibited suppressed cell proliferation, inflammation and induced apoptosis. PVT1 was predominately localized in the nucleus while evidence was obtained indicating that it could bind to the sirt6 promoter to induce sirt6 methylation, thus inhibiting sirt6 transcription. PVT1 knockdown was observed to restore sirt6 expression through decreasing sirt6 methylation, thereby alleviating RA. Conclusion The key findings of the study provide evidence suggesting that, PVT1 knockdown is able to restrain RA progression by inhibiting sirt6 methylation to restore its expression.