The Antiviral and Cancer Genomic DNA Deaminase APOBEC3H Is Regulated by an RNA-Mediated Dimerization Mechanism.

Human APOBEC3H and homologous single-stranded DNA cytosine deaminases are unique to mammals. These DNA-editing enzymes function in innate immunity by restricting the replication of viruses and transposons. APOBEC3H also contributes to cancer mutagenesis. Here, we address the fundamental nature of RNA in regulating human APOBEC3H activities. APOBEC3H co-purifies with RNA as an inactive protein, and RNase A treatment enables strong DNA deaminase activity. RNA-binding-defective mutants demonstrate clear separation of function by becoming DNA hypermutators. Biochemical and crystallographic data demonstrate a mechanism in which double-stranded RNA mediates enzyme dimerization. Additionally, APOBEC3H separation-of-function mutants show that RNA binding is required for cytoplasmic localization, packaging into HIV-1 particles, and antiviral activity. Overall, these results support a model in which structured RNA negatively regulates the potentially harmful DNA deamination activity of APOBEC3H while, at the same time, positively regulating its antiviral activity.

Epigenetic modification of a pectin methylesterase gene activates apoplastic iron reutilization in tomato roots.

Iron (Fe) distribution and reutilization are crucial for maintaining Fe homeostasis in plants. Here, we demonstrate that the tomato (Solanum lycopersicum) Colorless nonripening (Cnr) epimutant exhibits increased Fe retention in cell wall pectin due to an increase in pectin methylesterase (PME) activity. This ultimately leads to Fe deficiency responses even under Fe-sufficient conditions when compared to the wild type (WT). Whole-genome bisulfite sequencing revealed that modifications to cell wall-related genes, especially CG hypermethylation in the intron region of PECTIN METHYLESTERASE53 (SlPME53), are involved in the Cnr response to Fe deficiency. When this intron hypermethylation of SlPME53 was artificially induced in WT, we found that elevated SlPME53 expression was accompanied by increased PME activity and increased pectin-Fe retention. The manipulation of SlPME53, either through overexpression in WT or knockdown in Cnr, influenced levels of pectin methylesterification and accumulation of apoplast Fe in roots. Moreover, CG hypermethylation mediated by METHYLTRANSFERASE1 (SlMET1) increased SlPME53 transcript abundance, resulting in greater PME activity and higher Fe retention in cell wall pectin. Therefore, we conclude that the Cnr mutation epigenetically modulates SlPME53 expression by SlMET1-mediated CG hypermethylation, and thus the capacity of the apoplastic Fe pool, creating opportunities for genetic improvement of crop mineral nutrition.

Ten simple rules for computational biologists collaborating with wet lab researchers.

Computational biologists are frequently engaged in collaborative data analysis with wet lab researchers. These interdisciplinary projects, as necessary as they are to the scientific endeavor, can be surprisingly challenging due to cultural differences in operations and values. In this Ten Simple Rules guide, we aim to help dry lab researchers identify sources of friction and provide actionable tools to facilitate respectful, open, transparent, and rewarding collaborations.

Identification of pyruvic and maleic acid as potential markers for disease activity and prognosis in chronic urticaria.

BACKGROUND: Population-based studies have highlighted the link between chronic urticaria (CU) and metabolic syndrome, and metabolic alterations have been revealed in CU. However, to our knowledge, a comprehensive metabolomics study on a large cohort of patients with CU has not been reported. OBJECTIVE: We sought to explore the underlying metabolic subtypes and novel metabolite biomarkers for CU diagnosis and therapy. METHODS: Plasma samples from 80 patients with CU and 82 healthy controls were collected for metabolomics quantification and bioinformatics analysis. Another independent cohort consisting of 144 patients with CU was studied to validate the findings. Bone marrow-derived mast cells and mice with IgE-induced passive cutaneous anaphylaxis were used for in vitro and in vivo experiments, respectively. RESULTS: We observed clear metabolome differences between CU patients and healthy controls. Meanwhile, differential metabolites N6-acetyl-l-lysine, l-aspartate, maleic acid, and pyruvic acid were used to construct random forest classifiers and achieved area under receiver operating characteristic curve values greater than 0.85, suggesting their potential as diagnostic biomarkers of CU. More importantly, by exploring the underlying metabolic subtypes of CU, we found that the low abundance of pyruvic acid and maleic acid was significantly related to the activity of CU, poor efficacy of second-generation H1 antihistamines, and short relapse-free time. The results were validated in the independent cohort. Moreover, supplementation with pyruvate or maleate could significantly attenuate IgE-mediated mast cell activation in vitro and in vivo. CONCLUSIONS: Plasma pyruvic acid and maleic acid may be effective biomarkers for predicting disease activity, therapeutic efficacy, and prognosis for patients with CU.

Deep learning-guided adjuvant chemotherapy selection for elderly patients with breast cancer.

PURPOSE: The efficacy of adjuvant chemotherapy in elderly breast cancer patients is currently controversial. This study aims to provide personalized adjuvant chemotherapy recommendations using deep learning (DL). METHODS: Six models with various causal inference approaches were trained to make individualized chemotherapy recommendations. Patients who received actual treatment recommended by DL models were compared with those who did not. Inverse probability treatment weighting (IPTW) was used to reduce bias. Linear regression, IPTW-adjusted risk difference (RD), and SurvSHAP(t) were used to interpret the best model. RESULTS: A total of 5352 elderly breast cancer patients were included. The median (interquartile range) follow-up time was 52 (30-80) months. Among all models, the balanced individual treatment effect for survival data (BITES) performed best. Treatment according to following BITES recommendations was associated with survival benefit, with a multivariate hazard ratio (HR) of 0.78 (95% confidence interval (CI): 0.64-0.94), IPTW-adjusted HR of 0.74 (95% CI: 0.59-0.93), RD of 12.40% (95% CI: 8.01-16.90%), IPTW-adjusted RD of 11.50% (95% CI: 7.16-15.80%), difference in restricted mean survival time (dRMST) of 12.44 (95% CI: 8.28-16.60) months, IPTW-adjusted dRMST of 7.81 (95% CI: 2.93-11.93) months, and p value of the IPTW-adjusted Log-rank test of 0.033. By interpreting BITES, the debiased impact of patient characteristics on adjuvant chemotherapy was quantified, which mainly included breast cancer subtype, tumor size, number of positive lymph nodes, TNM stages, histological grades, and surgical type. CONCLUSION: Our results emphasize the potential of DL models in guiding adjuvant chemotherapy decisions for elderly breast cancer patients.

Multifunctional Carbon Dots for Biomedical Applications: Diagnosis, Therapy, and Theranostic.

Designing suitable nanomaterials is an ideal strategy to enable early diagnosis and effective treatment of diseases. Carbon dots (CDs) are luminescent carbonaceous nanoparticles that have attracted considerable attention. Through facile synthesis, they process properties including tunable light emission, low toxicity, and light energy transformation, leading to diverse applications as optically functional materials in biomedical fields. Recently, their potentials have been further explored, such as enzyme-like activity and ability to promote osteogenic differentiation. Through refined synthesizing strategies carbon dots, a rich treasure trove for new discoveries, stand a chance to guide significant development in biomedical applications. In this review, the authors start with a brief introduction to CDs. By presenting mechanisms and examples, the authors focus on how they can be used in diagnosing and treating diseases, including bioimaging failure of tissues and cells, biosensing various pathogenic factors and biomarkers, tissue defect repair, anti-inflammation, antibacterial and antiviral, and novel oncology treatment. The introduction of the application of integrated diagnosis and treatment follows closely behind. Furthermore, the challenges and future directions of CDs are discussed. The authors hope this review will provide critical perspectives to inspire new discoveries on CDs and prompt their advances in biomedical applications.

Proximity-Dependent Activation of Split DNAzyme Kinase.

Binary (also known as split) nucleic acid enzymes have emerged as novel tools in biosensors. We report a new split strategy to split the DNAzyme kinase into two independent and non-functional fragments, denoted DK1sub and DK1enz. In the presence of the specific target, their free ends are brought sufficiently close to interact with each other without the formation of Watson-Crick base pairings between Dk1sub and Dk1enz, thus allowing the DNA phosphorylation reaction. We term this approach proximity-dependent activation of split DNAzyme kinase (ProxSDK). The utility of ProxSDK is demonstrated by engineering a biosensing system that is capable of measuring specific DNA-protein interactions. We envision that the approach described herein will find useful applications in biosensing, imaging, and clinical diagnosis.

StreamSAXS: a Python-based workflow platform for processing streaming SAXS/WAXS data.

StreamSAXS is a Python-based small- and wide-angle X-ray scattering (SAXS/WAXS) data analysis workflow platform with graphical user interface (GUI). It aims to provide an interactive and user-friendly tool for analysis of both batch data files and real-time data streams. Users can easily create customizable workflows through the GUI to meet their specific needs. One characteristic of StreamSAXS is its plug-in framework, which enables developers to extend the built-in workflow tasks. Another feature is the support for both already acquired and real-time data sources, allowing StreamSAXS to function as an offline analysis platform or be integrated into large-scale acquisition systems for end-to-end data management. This paper presents the core design of StreamSAXS and provides user cases demonstrating its utilization for SAXS/WAXS data analysis in offline and online scenarios.

WTAP-mediated m6A modification of lncRNA Snhg1 improves myocardial ischemia-reperfusion injury via miR-361-5p/OPA1-dependent mitochondrial fusion.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is caused by reperfusion after ischemic heart disease. LncRNA Snhg1 regulates the progression of various diseases. N6-methyladenosine (m6A) is the frequent RNA modification and plays a critical role in MIRI. However, it is unclear whether lncRNA Snhg1 regulates MIRI progression and whether the lncRNA Snhg1 was modified by m6A methylation. METHODS: Mouse cardiomyocytes HL-1 cells were utilized to construct the hypoxia/reoxygenation (H/R) injury model. HL-1 cell viability was evaluated utilizing CCK-8 method. Cell apoptosis, mitochondrial reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were quantitated utilizing flow cytometry. RNA immunoprecipitation and dual-luciferase reporter assays were applied to measure the m6A methylation and the interactions between lncRNA Snhg1 and targeted miRNA or target miRNAs and its target gene. The I/R mouse model was constructed with adenovirus expressing lncRNA Snhg1. HE and TUNEL staining were used to evaluate myocardial tissue damage and apoptosis. RESULTS: LncRNA Snhg1 was down-regulated after H/R injury, and overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization. Besides, lncRNA Snhg1 could target miR-361-5p, and miR-361-5p targeted OPA1. Overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization though the miR-361-5p/OPA1 axis. Furthermore, WTAP induced lncRNA Snhg1 m6A modification in H/R-stimulated HL-1 cells. Moreover, enforced lncRNA Snhg1 repressed I/R-stimulated myocardial tissue damage and apoptosis and regulated the miR-361-5p and OPA1 levels. CONCLUSION: WTAP-mediated m6A modification of lncRNA Snhg1 regulated MIRI progression through modulating myocardial apoptosis, mitochondrial ROS production, and mitochondrial polarization via miR-361-5p/OPA1 axis, providing the evidence for lncRNA as the prospective target for alleviating MIRI progression.

Rab32 facilitates Schwann cell pyroptosis in rats following peripheral nerve injury by elevating ROS levels.

BACKGROUND: Peripheral nerve injury (PNI) is commonly observed in clinical practice, yet the underlying mechanisms remain unclear. This study investigated the correlation between the expression of a Ras-related protein Rab32 and pyroptosis in rats following PNI, and potential mechanisms have been explored by which Rab32 may influence Schwann cells pyroptosis and ultimately peripheral nerve regeneration (PNR) through the regulation of Reactive oxygen species (ROS) levels. METHODS: The authors investigated the induction of Schwann cell pyroptosis and the elevated expression of Rab32 in a rat model of PNI. In vitro experiments revealed an upregulation of Rab32 during Schwann cell pyroptosis. Furthermore, the effect of Rab32 on the level of ROS in mitochondria in pyroptosis model has also been studied. Finally, the effects of knocking down the Rab32 gene on PNR were assessed, morphology, sensory and motor functions of sciatic nerves, electrophysiology and immunohistochemical analysis were conducted to assess the therapeutic efficacy. RESULTS: Silencing Rab32 attenuated PNI-induced Schwann cell pyroptosis and promoted peripheral nerve regeneration. Furthermore, our findings demonstrated that Rab32 induces significant oxidative stress by damaging the mitochondria of Schwann cells in the pyroptosis model in vitro. CONCLUSION: Rab32 exacerbated Schwann cell pyroptosis in PNI model, leading to delayed peripheral nerve regeneration. Rab32 can be a potential target for future therapeutic strategy in the treatment of peripheral nerve injuries.

Exogenous putrescine plays a switch-like influence on the pH stress adaptability of biofilm-based activated sludge.

Microbial community adaptability to pH stress plays a crucial role in biofilm formation. This study aims to investigate the regulatory mechanisms of exogenous putrescine on pH stress, as well as enhance understanding and application for the technical measures and molecular mechanisms of biofilm regulation. Findings demonstrated that exogenous putrescine acted as a switch-like distributor affecting microorganism pH stress, thus promoting biofilm formation under acid conditions while inhibiting it under alkaline conditions. As pH decreases, the protonation degree of putrescine increases, making putrescine more readily adsorbed. Protonated exogenous putrescine could increase cell membrane permeability, facilitating its entry into the cell. Subsequently, putrescine consumed intracellular H+ by enhancing the glutamate-based acid resistance strategy and the γ-aminobutyric acid metabolic pathway to reduce acid stress on cells. Furthermore, putrescine stimulated ATPase expression, allowing for better utilization of energy in H+ transmembrane transport and enhancing oxidative phosphorylation activity. However, putrescine protonation was limited under alkaline conditions, and the intracellular H+ consumption further exacerbated alkali stress and inhibits cellular metabolic activity. Exogenous putrescine promoted the proportion of fungi and acidophilic bacteria under acidic stress and alkaliphilic bacteria under alkali stress while having a limited impact on fungi in alkaline biofilms. Increasing Bdellovibrio under alkali conditions with putrescine further aggravated the biofilm decomposition. This research shed light on the unclear relationship between exogenous putrescine, environmental pH, and pH stress adaptability of biofilm. By judiciously employing putrescine, biofilm formation could be controlled to meet the needs of engineering applications with different characteristics.IMPORTANCEThe objective of this study is to unravel the regulatory mechanism by which exogenous putrescine influences biofilm pH stress adaptability and understand the role of environmental pH in this intricate process. Our findings revealed that exogenous putrescine functioned as a switch-like distributor affecting the pH stress adaptability of biofilm-based activated sludge, which promoted energy utilization for growth and reproduction processes under acidic conditions while limiting biofilm development to conserve energy under alkaline conditions. This study not only clarified the previously ambiguous relationship between exogenous putrescine, environmental pH, and biofilm pH stress adaptability but also offered fresh insights into enhancing biofilm stability within extreme environments. Through the modulation of energy utilization, exerting control over biofilm growth and achieving more effective engineering goals could be possible.

A Prospective Randomized Trial of Neoadjuvant Chemohormonal Therapy vs Hormonal Therapy in Locally Advanced Prostate Cancer Treated by Radical Prostatectomy.

PURPOSE: Benefits of docetaxel-based neoadjuvant chemohormonal therapy (NCHT) before radical prostatectomy (RP) remain largely unknown. We explored whether docetaxel-based NCHT would bring pathological benefits and improve biochemical progression-free survival (bPFS) over neoadjuvant hormonal therapy (NHT) in locally advanced prostate cancer. MATERIALS AND METHODS: A randomized trial was designed recruiting 141 locally advanced, high-risk prostate cancer patients who were randomly assigned at the ratio of 2:1 to the NCHT group (75 mg/m2 body surface area every 3 weeks plus androgen deprivation therapy for 6 cycles) and the NHT group (androgen deprivation therapy for 24 weeks). The primary end point was 3-year bPFS. Secondary end points were pathological response including pathological downstaging and minimal residual disease rates. RESULTS: The NCHT group showed significant benefits in 3-year bPFS compared to the NHT group (29% vs 9.5%, P = .002). At a median follow-up of 53 months, the NCHT group achieved a significantly longer median bPFS time than the NHT group (17 months vs 14 months). No significant differences were found between the 2 groups in pathological downstaging and minimal residual disease rates. CONCLUSIONS: NCHT plus RP achieved significant bPFS benefits when compared with NHT plus RP in high-risk, locally advanced prostate cancer. A larger cohort with longer follow-up duration is essential in further investigation.

Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) causes neurological disease in the peripheral and central nervous system (PNS and CNS, respectively) of some patients. It is not clear whether SARS-CoV-2 infection or the subsequent immune response are the key factors that cause neurological disease. Here, we addressed this question by infecting human induced pluripotent stem cell-derived CNS and PNS neurons with SARS-CoV-2. SARS-CoV-2 infected a low number of CNS neurons and did not elicit a robust innate immune response. On the contrary, SARS-CoV-2 infected a higher number of PNS neurons. This resulted in expression of interferon (IFN) λ1, several IFN-stimulated genes and proinflammatory cytokines. The PNS neurons also displayed alterations characteristic of neuronal damage, as increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and α-synuclein, and lower levels of cytoskeletal proteins. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neuronal damage, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS. Our results provide a basis to study coronavirus disease 2019 (COVID-19) related neuronal pathology and to test future preventive or therapeutic strategies.

Varicella zoster virus-induced autophagy in human neuronal and hematopoietic cells exerts antiviral activity.

Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defense mechanism is recognized and some viruses hijack and modulate this process to their advantage in certain cell types. Here, we present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH-SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV-infected SH-SY5Y cells showed increased LC3-I-LC3-II conversion as well as co-localization of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with severe ocular and brain VZV infection were analyzed to identify potential autophagy-associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV-infected cells. In conclusion, these results demonstrate a neuro-protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease.

A fluorescent probe based on cyclochalcone for detecting peroxynitrite.

A novel cyclic chalcone fluorescent probe C-PN was synthesized to detect ONOO-. After reaction with peroxynitrite, the double bond of C-PN in the cyclic chalcone structure was disconnected, which caused the change of intramolecular charge transfer (ICT) effect, emitting blue fluorescence and quenching orange red fluorescence. Visible to the naked eye, the color of the probe solution changed. The probe showed low sensitivity (detection limit = 20.2 nm), short response time (less than 60 s) at low concentration of ONOO-, good visibility, and good selectivity and stability for ONOO-.

t-BuOLi promoted regioselective N-thiolation of indoles with N-arylthio phthalimide.

The selective N-thiolation of indole substrates poses a challenge due to their diminished nucleophilicity at nitrogen. Herein, we present a novel method for the thiolation of the NH group in indole derivatives by using N-arylthio phthalimide as the sulfur source, t-BuOLi as the base and MeCN as the solvent. The process was successfully conducted under transition metal catalyst-free and room temperature conditions with a high product yield and a short reaction time. The developed protocol exhibited excellent regioselectivity and broad substrate tolerance in the preparation of N-thioindoles with diverse functional groups.

Nuclear proteins and diabetic retinopathy: a review.

Diabetic retinopathy (DR) is an eye disease that causes blindness and vision loss in diabetic. Risk factors for DR include high blood glucose levels and some environmental factors. The pathogenesis is based on inflammation caused by interferon and other nuclear proteins. This review article provides an overview of DR and discusses the role of nuclear proteins in the pathogenesis of the disease. Some core proteins such as MAPK, transcription co-factors, transcription co-activators, and others are part of this review. In addition, some current advanced treatment resulting from the role of nuclear proteins will be analyzes, including epigenetic modifications, the use of methylation, acetylation, and histone modifications. Stem cell technology and the use of nanobiotechnology are proposed as promising approaches for a more effective treatment of DR.

Punicalagin attenuates TNF-α-induced oxidative damage and promotes osteogenic differentiation of bone mesenchymal stem cells by activating the Nrf2/HO-1 pathway.

Oxidative stress is one of the most important factors in changing bone homeostasis. Redox homeostasis plays a key role in the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) and the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) for bone regeneration. Currently, this study assessed the effects of punicalagin (PUN) on BMSCs and HUVECs. Cell viability was determined by CCK-8 assay. A flow cytometry analysis was adopted to detect macrophage polarization. The production of reactive oxygen stress (ROS), glutathione (GSH), malonaldehyde (MDA) and superoxide dismutase (SOD) activities were evaluated by using commercially-available kits. Osteogenic capacity of BMSCs was evaluated by ALP activity, ALP staining and ARS staining. The expression of osteogenic-related proteins (OCN, Runx-2, OPN) and Nrf/HO-1 levles were evaluated by Western blotting. Osteogenic-related genes (Osterix, COL-1, BMP-4, ALP) were evaluated by RT-PCR. Migration ability and invasion ability of HUVECs were evaluated by wound healing assay and Transwell assay. Angiogenic ability was detected by tube formation assay and the expression of angiogenic-related genes (VEGF, vWF, CD31) were evaluated by RT-PCR. Results showed that PUN alleviated oxidative stress by TNF-α, enhanced osteogenic differentiation in BMSCs and angiogenesis in HUVECs. Moreover, PUN regulate immune microenvironment by promoting the polarization of M2 macrophages and reduce the oxidative stress related products by activating Nrf2/HO-1 pathway. Altogether, these results suggested that PUN can promote osteogenic capacity of BMSCs, angiogenesis of HUVECs, alleviate oxidative stress via Nrf2/HO-1 pathway, offering PUN as a novel antioxidant agent for treating bone loss diseases.

A new strategy for the treatment of Parkinson's disease: Discovery and bio-evaluation of the first central-targeting tyrosinase inhibitor.

The high level of tyrosinase leads to the generation of neuromelanin, further causing the abnormality of redox-related protein level and mediating the occurrence and development of Parkinson's disease (PD). However, the existing tyrosinase inhibitors are mostly natural product extracts or polyphenolic derivatives, which hindered them from penetrating the blood-brain barrier (BBB). Herein, we obtained a novel tyrosinase inhibitor, 2-06 (tyrosinase: monophenolase IC50 = 70.44 ± 22.69 µM, diphenolase IC50 = 1.89 ± 0.64 µM), through the structure-based screening method. The compound 2-06 presented good in vitro and in vivo safety, and can inhibit the tyrosinase and melanogenesis in B16F10. Moreover, this compound showed neuroprotective effects and Parkinsonism behavior improving function. 2-06 was proved to penetrate the BBB and enter the central nervous system (CNS). The exploration of the binding mode between 2-06 and tyrosinase provided the foundation for the subsequent structural optimization. This is the first research to develop a central-targeting tyrosinase inhibitor, which is crucial for in-depth study on the new strategy for utilizing tyrosinase inhibitors to treat PD.

A positive feedback circuit between RN7SK snRNA and m6A readers is essential for tumorigenesis.

N6-Methyladenosine (m6A) RNA modification, methylation at the N6 position of adenosine, plays critical roles in tumorigenesis. m6A readers recognize m6A modifications and thus act as key executors for the biological consequences of RNA methylation. However, knowledge about the regulatory mechanism(s) of m6A readers is extremely limited. In this study, RN7SK was identified as a small nuclear RNA that interacts with m6A readers. m6A readers recognized and facilitated secondary structure formation of m6A-modified RN7SK, which in turn prevented m6A reader mRNA degradation from exonucleases. Thus, a positive feedback circuit between RN7SK and m6A readers is established in tumor cells. From findings on the interaction with RN7SK, new m6A readers, such as EWS RNA binding protein 1 (EWSR1) and KH RNA binding domain containing, signal transduction-associated 1 (KHDRBS1), were identified and shown to boost Wnt/ß-catenin signaling and tumorigenesis by suppressing translation of Cullin1 (CUL1). Moreover, several Food and Drug Administration-approved small molecules were demonstrated to reduce RN7SK expression and inhibit tumorigenesis. Together, these findings reveal a common regulatory mechanism of m6A readers and indicate that targeting RN7SK has strong potential for tumor treatment.