Biology subjects

Zeng, C.

Publications and source records attributed to Zeng, C..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Au18(L-NIBC)14 targets ASC oligomerization for autoimmune disease treatment

Gold nanoclusters (AuNCs), unlike conventional nanoparticles, possess molecular characteristics besides ultrasmall nano-features. Recently, we and others showed that AuNCs are promising in treatments of various major diseases. However, the AuNCs used were usually mixtures, and the specific target and their relationship with AuNC structures are unclear, which largely restrict their druggability. Multiple sclerosis (MS) is an autoimmune disease (AID) implicating central nervous system (CNS), in which drug discovery is challenging. Here we used Au18(L-N-isobutyryl-L-cysteine)14 (Au18(L-NIBC)14) and Au25(L-NIBC)18, two AuNCs with the same ligand, to report their much different therapeutic effects in experimental autoimmune encephalomyelitis (EAE). We show that, Au18(L-NIBC)14, but not Au25(L-NIBC)18, specifically targets apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, thus inhibit the activation of ASC-dependent inflammasomes, resulting in comprehensive restoration of cytokine homeostasis in the CNS of EAE mice. Au18(L-NIBC)14 significantly prevents axon demyelination, protects blood-brain barrier, blocks immune cell infiltration into CNS, and completely prevents motor deficits and relieve the early-cognitive impairments of EAE mice. Remarkable efficacies were also observed in animal models of inflammatory bowel disease, psoriasis, systemic lupus erythematosus, indicating a broad prospect in AIDs treatments. Especially, definite molecular structure, specific target, clear mechanism, and exact therapeutic effects imply a good druggability of Au18(L-NIBC)14.

pharmacology and toxicology↗

bioRxiv2025

A SET domain-containing protein and HCF-1 maintain transgenerational epigenetic memory

Epigenetic information can be inherited through a process known as transgenerational epigenetic inheritance (TEI). TEI can be initiated and maintained by small RNAs and histone modifications. The latter includes histone methylation, deposited by proteins with methyltransferase activity, including SET domain-containing proteins. Other SET domain-containing proteins with no catalytic methyltransferase activity also adopt roles in chromatin and gene expression regulation. Here, we describe SET-24, a SET domain-containing protein in Caenorhabditis elegans that belongs to a family of catalytically inactive SET proteins. SET-24 localises to germline nuclei and is required for germline immortality. Additionally, the inheritance of small RNA-driven epigenetic silencing is compromised in set-24 mutants. Using quantitative proteomics and yeast two-hybrid assays, we found that SET-24 interacts with Host Cell Factor 1 (HCF-1), a protein involved in epigenetic regulation and associated with known chromatin remodelling complexes, like COMPASS, which deposits H3K4me3. In set-24 mutants, hundreds of genes display increased H3K4me3 levels at their transcription start sites. While these changes are not matched at the transcriptional level, small RNA production is disrupted in approximately one fifth of those genes, which are normally targeted by small RNA pathways. We propose that SET-24 is a factor required to maintain epigenetic memory in the germline by maintaining a chromatin environment permissible to small RNA biogenesis over generations.

molecular biology↗

bioRxiv2025

Quinpirole ameliorates the dysfunction of microglia in human LRRK2-R1441G transgenic mice

Microglia-mediated neuroinflammation is a key contributor to Parkinsons disease (PD) pathogenesis. Leucine-rich repeat kinase 2 (LRRK2), the leading genetic contributor to both familial and sporadic PD, has been implicated in driving this connection. However, its precise role remains incompletely understood due to technical challenges. To address this, we utilized a bacterial artificial chromosome (BAC) transgenic mouse model overexpressing human LRRK2-R1441G, which replicates key features of PD. These mice were crossed with Cx3cr1-EGFP mice to enable assessment of microglial dynamics and function using two-photon imaging in awake mice in vivo and acute brain slices ex vivo. Furthermore, spatial transcriptomic analysis was performed using GeoMx Digital Spatial Profiler technology to compare transgenic mice with their wild-type counterparts. The R1441G mutation upregulated antigen processing and presentation pathways, increased activated microglia, and enhanced microglial polarization in the dorsal striatum. Mutant microglia exhibited reduced motility and slower responses to focal injury, with processes retracting faster and extending more slowly. Quinpirole, a dopamine D2 receptor (D2R) agonist, successfully reversed microglial deficits. This study provides the first evidence that pathogenic LRRK2 mutations alter microglial motility and responsiveness in vivo, highlighting D2R activation as a promising therapeutic strategy to mitigate neuroinflammation and neurodegeneration in PD.

neuroscience↗

bioRxiv2025

Single-cell multiome and spatial profiling reveals pancreas cell type-specific gene regulatory programs driving type 1 diabetes progression

Cell type-specific regulatory programs that drive type 1 diabetes (T1D) in the pancreas are poorly understood. Here we performed single nucleus multiomics and spatial transcriptomics in up to 32 non-diabetic (ND), autoantibody-positive (AAB+), and T1D pancreas donors. Genomic profiles from 853,005 cells mapped to 12 pancreatic cell types, including multiple exocrine sub- types. Beta, acinar, and other cell types, and related cellular niches, had altered abundance and gene activity in T1D progression, including distinct pathways altered in AAB+ compared to T1D. We identified epigenomic drivers of gene activity in T1D and AAB+ which, combined with genetic association, revealed causal pathways of T1D risk including antigen presentation in beta cells. Finally, single cell and spatial profiles together revealed widespread changes in cell-cell signaling in T1D including signals affecting beta cell regulation. Overall, these results revealed drivers of T1D progression in the pancreas, which form the basis for therapeutic targets for disease prevention.

genomics↗

bioRxiv2024

An antibiotic that mediates immune destruction of senescent cancer cells

Drugs that eliminate senescent cells, senolytics, can be powerful when combined with pro-senescence cancer therapies. Using a CRISPR/Cas9-based genetic screen, we identify here SLC25A23 as a vulnerability of senescent cancer cells. Suppressing SLC25A23 disrupts cellular calcium homeostasis, impairs oxidative phosphorylation and interferes with redox signaling, leading to death of senescent cells. These effects can be replicated by salinomycin, a cation ionophore antibiotic. Salinomycin prompts a PANoptosis-like cell death in senescent cells, including apoptosis and two forms of immunogenic cell death: necroptosis and pyroptosis. Notably, we observed that salinomycin treatment or SLC25A23 suppression elevates reactive oxygen species, upregulating death receptor 5 via JNK pathway activation. We show that a combination of a DR5 agonistic antibody and salinomycin is a robust senolytic cocktail. We provide evidence that this drug combination provokes a potent NK and CD8+ T cell mediated immune destruction of senescent cancer cells, mediated by the pyroptotic cytokine IL18. SignificanceThe efficacy of multiple cancer drugs is limited by the induction of senescence, which enables cancer cells to evade cell death. We uncover here a new selective vulnerability of senescent cancer cells and we show that this vulnerability can be targeted with a commonly-used antibiotic. We show that a combination of senescence-inducing therapy, combined with this antibiotic causes a highly immunogenic cell death phenotype that further stimulates potent immune destruction of senescent cancer cells.

cancer biology↗

bioRxiv2024

Genetic diversity analysis of main agronomic traits and ISSR markers in 35 ornamental rape germplasm resources

Rape (Brassica napus L.) is a major oil crop in our country, valued for its oil and ornamental uses. This study analyzed 35 ornamental rape germplasm resources from different origins to examine differences in agronomic traits and molecular markers. Nine agronomic traits were assessed in the field for variability, correlation, principal component analysis, and cluster analysis. Genetic diversity was analyzed using microsatellite (ISSR) markers and the unweighted pair group method with arithmetic mean (UPGMA). Our findings revealed a notable average coefficient of variation of 22.59% across the nine agronomic traits, with flower color exhibiting the highest variability and corolla width the least. The observed range of variation spanned from 9.24% to 83.38%, the correlation among these traits was generally low, with a mere 13.9% demonstrating significant correlations. The four principal components accounted for an impressive 84.62% of the cumulative contribution rate, while the genetic similarity, as gauged by eight ISSR primers, varied from 0.675 to 0.980. Most strikingly, we observed that plants from the same geographical region displayed molecular-level differences, underscoring the rich genetic diversity inherent in the 35 ornamental rape resources under study. Employing UPGMA cluster analysis on the primary agronomic traits and ISSR molecular markers, the 35 ornamental rape resources were categorized into seven and four distinct groups, respectively. Although the clustering outcomes from these two methodologies did not align perfectly, they served to complement each other. Collectively, these insights offer a theoretical framework for the innovation of ornamental rape germplasm resources and the cultivation of novel varieties.

genetics↗

bioRxiv2024

A broad cathepsin inhibitor blocks crystal-stimulated inflammasome-dependent and -independent inflammation, and gout arthritis

In the disease gout, monosodium urate (MSU) crystals nucleate in joints and cause acute painful arthritis that can damage the affected joints. Similarly, the deposition of other crystals or irritant particles in tissues elicits an inflammatory response that can cause disease. These various particles stimulate macrophages to produce the proinflammatory cytokine interleukin 1{beta} (IL-1{beta}), which is a major driver of the ensuing inflammation. Here we show that in vivo and in vitro, broad spectrum cathepsin inhibitors, like VBY-825, blocked the activation of inflammasomes, which are known to be essential in generating bioactive IL-1{beta} in response to crystals. In addition, the cathepsin inhibitors blocked an inflammasome-independent pathway that also generates mature IL-1{beta} and which contributed substantially to crystal-stimulated inflammation in vivo. Through these effects, the cathepsin inhibitors markedly reduced gout arthritis and inflammation to the unrelated crystal silica, which is the etiologic agent in the disease silicosis. The cathepsin inhibitors didnt affect any of the inflammatory processes after bioactive IL-1{beta} was present in tissues. They also didnt inhibit LPS-stimulated inflammation in mice, or TNF- production from macrophages. These findings provide proof of concept that cathepsin inhibitors are a novel class of anti-inflammatories that can inhibit crystal-stimulated disease with unique mechanisms of action.

immunology↗

bioRxiv2024

Different Emotional States Engage Distinct Descending Pathways from the Prefrontal Cortex

Effective emotional processing, crucial for adaptive behavior, is mediated by the medial prefrontal cortex (mPFC) via connections to the basolateral amygdala (BLA) and nucleus accumbens (NAc), traditionally considered functionally similar in modulating reward and aversion responses. However, the functional specialization of the mPFC[->]BLA and mPFC[->]NAc pathways in representing affective states remains unclear. We found that while overall firing patterns appeared consistent across emotional states, deeper analysis revealed distinct variabilities. Specifically, mPFC[->]BLA neurons, especially "center-ON" neurons, exhibited heightened activity during behaviors classically associated with anxiety-like states, suggesting their involvement in aversive behavioral regulation. Conversely, mPFC[->]NAc neurons were more active during exploratory and approach-related behaviors, implicating them in the processing of positively valenced behavioral states. Notably, mPFC[->]NAc neurons showed significant pattern decorrelation during social interactions, suggesting a pivotal role in processing social preference. Additionally, repeated win/loss outcomes in the tube test produced distinct hierarchy-dependent behavioral changes and elevated corticosterone levels in loser mice, supporting the biological relevance of these behaviorally defined states. Together, these findings reveal pathway-specific representations of affect-related behavioral states in mPFC circuits and provide a framework for understanding how prefrontal outputs organize adaptive behavior across environmental contexts.

neuroscience↗

bioRxiv2024

Gut Microbiome-Driven Metabolites Influence Skin Pigmentation in TYRP1 Mutant Oujiang Color Common Carp

The gut microbiome is one of the major regulators of the gut-skin axis and is partly regulated by host genetics. In the present study, using comparative high-throughput omics data on CRISPR/Cas9-mediated TYRP1 mutant and wild-color common carp populations, we quantified the proportion of inter-individual variation in the skin transcriptome and blood metabolome by genetic architecture and gut microbiomes. We found 525 differential metabolites (DMs) and 45 differential gut microbial genera in TYRP1 mutant fishes relative to the wild type. Through interaction analysis and causal mediation analyses, we revealed that the TYRP1-mutant derived genetic background may exert an inflammatory Acinetobacter - Leukotrience-C4 and - Spermine metabolic pathway under the regulation of an anti-inflammatory cardio-vascular genetic network underlying the upregulating expression of COMT, PLG, C2, C3, F10, TDO2, MHC1, and SERPINF2 gene for evolving unusual coffee-like color phenotype. This unique network appears to underlie the "coffee-like" color phenotype. We propose that the COMT-mediated causal effect of the unusual gut microbiome on the atypical skin gene expression patterns through the gut-skin metabolic pathway. Article SummaryR.N. Mandal et al. report on the causal effect of gut microbiome-driven metabolites on the expression pattern of regulatory genes underlying an unusual color phenotype. It suggests that TYRP1 Mutation may rise an unusual inflammatory gut microbiome-skin metabolic pathway that may be balanced by an anti-inflammatory cardio-vascular genetic network leading to unique coloration in Oujiang Color Common Carp.

genetics↗

bioRxiv2024

Metabolic control of adaptive β-cell proliferation by the protein deacetylase SIRT2

Selective and controlled expansion of endogenous {beta}-cells has been pursued as a potential therapy for diabetes. Ideally, such therapies would preserve feedback control of {beta}-cell proliferation to avoid excessive {beta}-cell expansion and an increased risk of hypoglycemia. Here, we identified a regulator of {beta}-cell proliferation whose inactivation results in controlled {beta}-cell expansion: the protein deacetylase Sirtuin 2 (SIRT2). Sirt2 deletion in {beta}-cells of mice increased {beta}-cell proliferation during hyperglycemia with little effect in homeostatic conditions, indicating preservation of feedback control of {beta}-cell mass. SIRT2 restrains proliferation of human islet {beta}-cells cultured in glucose concentrations above the glycemic set point, demonstrating conserved SIRT2 function. Analysis of acetylated proteins in islets treated with a SIRT2 inhibitor revealed that SIRT2 deacetylates enzymes involved in oxidative phosphorylation, dampening the adaptive increase in oxygen consumption during hyperglycemia. At the transcriptomic level, Sirt2 inactivation has context-dependent effects on {beta}-cells, with Sirt2 controlling how {beta}-cells interpret hyperglycemia as a stress. Finally, we provide proof-of-principle that systemic administration of a GLP1-coupled Sirt2-targeting antisense oligonucleotide achieves {beta}-cell selective Sirt2 inactivation and stimulates {beta}-cell proliferation under hyperglycemic conditions. Overall, these studies identify a therapeutic strategy for increasing {beta}-cell mass in diabetes without circumventing feedback control of {beta}-cell proliferation.

physiology↗

bioRxiv2023

Inflammation primes the kidney for recovery by activating AZIN1 A-to-I editing

The progression of kidney disease varies among individuals, but a general methodology to quantify disease timelines is lacking. Particularly challenging is the task of determining the potential for recovery from acute kidney injury following various insults. Here, we report that quantitation of post-transcriptional adenosine-to-inosine (A-to-I) RNA editing offers a distinct genome-wide signature, enabling the delineation of disease trajectories in the kidney. A well-defined murine model of endotoxemia permitted the identification of the origin and extent of A-to-I editing, along with temporally discrete signatures of double-stranded RNA stress and Adenosine Deaminase isoform switching. We found that A-to-I editing of Antizyme Inhibitor 1 (AZIN1), a positive regulator of polyamine biosynthesis, serves as a particularly useful temporal landmark during endotoxemia. Our data indicate that AZIN1 A-to-I editing, triggered by preceding inflammation, primes the kidney and activates endogenous recovery mechanisms. By comparing genetically modified human cell lines and mice locked in either A-to-I edited or uneditable states, we uncovered that AZIN1 A-to-I editing not only enhances polyamine biosynthesis but also engages glycolysis and nicotinamide biosynthesis to drive the recovery phenotype. Our findings implicate that quantifying AZIN1 A-to-I editing could potentially identify individuals who have transitioned to an endogenous recovery phase. This phase would reflect their past inflammation and indicate their potential for future recovery.

molecular biology↗

bioRxiv2023

High plasticity of ribosomal DNA organization in budding yeast

In eukaryotic genomes, ribosomal DNA (rDNA) generally resides as a highly repetitive and dynamic structure, making it difficult to study. Here, a synthetic rDNA array on chromosome III in budding yeast was constructed to serve as the sole source of rRNA. Utilizing the loxPsym site within each rDNA repeat and the Cre recombinase, we were able to reduce the copy number to as few as eight copies. Additionally, we constructed strains with two or three rDNA arrays, and found that the presence of multiple arrays did not affect the formation of a single nucleolus. Although alteration on the position and number of rDNA arrays did impact three-dimensional genome structure, the additional rDNA arrays had no deleterious influence on cell growth or transcriptomes. Together, this study sheds light on the high plasticity of rDNA organization and opens up opportunities for future rDNA engineering. HighlightsO_LIA method was established for efficient construction of synthetic rDNA arrays in budding yeast C_LIO_LIThe rDNA repeats in a haploid yeast can be reduced to as few as eight copies to support cell viability C_LIO_LIYeast cells with two or three DNA arrays on distinct chromosomes form a single nucleolus. C_LIO_LIDispersed rDNA arrays result in no deleterious influence on cell growth or transcriptomes. C_LI

synthetic biology↗

bioRxiv2023

SeMOE allows for quantitative glycan perception and exhibits anti-cancer potentiality

Metabolic oligosaccharide engineering (MOE) is a classical chemical approach to perturb, profile and perceive glycans in physiological systems, but probes upon bioorthogonal reaction require accessibility and background signal readout makes it challenging to achieve absolute glycan quantification. Here we develop SeMOE, a selenosugar-based metabolic oligosaccharide engineering strategy that combines elemental analysis and MOE to enable the absolute quantification and mass spectrometric imaging of glycome in a concise procedure. We demonstrate that SeMOE probes allow for perception, absolute quantification and visualization of glycans in diverse biological contexts. We demonstrate that chemical reporters on conventional MOE can be integrated into a bifunctional SeMOE probe to provide multimodality signal readouts. We further show the anti-cancer potentiality of SeMOE probes. SeMOE thus provides a convenient and simplified method to "see more" of the glyco-world.

bioengineering↗

bioRxiv2023

Semiconductor augumented valuable chemical photosynthesis from Rhodospirillum rubrum and mechanism study

Photosynthetic biohybrid systems based on purple bacteria and semiconducting nanomaterials are promising platforms for sustainable solar-powered chemical production. However, these types of biohybrid systems have not been fully developed to date, and their energy utilization and electron transfer mechanisms are not well understood. Herein, a Rhodospirillum rubrum-CdS biohybrid system was successfully constructed. The photosynthetic activity and photoelectrochemical properties of biohybrid system were analyzed. Chromatographic and spectroscopic studies confirmed the metabolic activities of R. rubrum cells were effectively augmented by surface-deposited CdS nanoparticles and validated with increased H2 evolution, polyhydroxybutyric acid (PHB) production, and solid biomass accumulation. Energy consumption and metabolic profiles of R. rubrum-CdS biohybrid system exhibited a growth phase-dependent behaviour. Photoelectrochemical study confirmed that light-excited electrons from CdS enhanced photosynthetic electron flow of R. rubrum cells. Monochromatic light modulated photoexcitation of biohybrid system was utilized to explore interfacial electron transfer between CdS and R. rubrum cells, and the results showed that CdS enhanced the utilization of blue light by R. rubrum cells. This work investigated the feasibility and prospect of utilizing R. rubrum in semi-artificial photosynthesis of valuable products, and offered insights into the energy utilization and the electron transfer mechanism between nanomaterials and purple bacteria.

microbiology↗

bioRxiv2023

Integration of single-cell multiomic measurements across disease states with genetics identifies mechanisms of beta cell dysfunction in type 2 diabetes

Altered function and gene regulation of pancreatic islet beta cells is a hallmark of type 2 diabetes (T2D), but a comprehensive understanding of mechanisms driving T2D is still missing. Here we integrate information from measurements of chromatin activity, gene expression and function in single beta cells with genetic association data to identify disease-causal gene regulatory changes in T2D. Using machine learning on chromatin accessibility data from 34 non-diabetic, pre-T2D and T2D donors, we robustly identify two transcriptionally and functionally distinct beta cell subtypes that undergo an abundance shift in T2D. Subtype-defining active chromatin is enriched for T2D risk variants, suggesting a causal contribution of subtype identity to T2D. Both subtypes exhibit activation of a stress-response transcriptional program and functional impairment in T2D, which is likely induced by the T2D-associated metabolic environment. Our findings demonstrate the power of multimodal single-cell measurements combined with machine learning for identifying mechanisms of complex diseases.

systems biology↗

bioRxiv2022

Searching across-cohort relatives via encrypted genotype regression

Explicitly sharing individual level data in genomics studies has many merits comparing to sharing summary statistics, including more strict QCs, common statistical analyses, relative identification and improved statistical power in GWAS, but it is hampered by privacy or ethical constraints. In this study, we developed encG-reg, a regression approach that can detect relatives of various degrees based on encrypted genomic data, which is immune of ethical constraints. The encryption properties of encG-reg are based on the random matrix theory by masking the original genotypic matrix without sacrificing precision of individual-level genotype data. We established a connection between the dimension of a random matrix, which masked genotype matrices, and the required precision of a study for encrypted genotype data. encG-reg has false positive and false negative rates equivalent to sharing original individual level data, and is computationally efficient when searching relatives. We split the UK Biobank into their respective centers, and then encrypted the genotype data. We observed that the relatives estimated using encG-reg was equivalently accurate with the estimation by KING, which is a widely used software but requires original genotype data. In a more complex application, we launched a finely devised multi-center collaboration across 5 research institutes in China, covering 9 cohorts of 54,092 GWAS samples. encG-reg again identified true relatives existing across the cohorts with even different ethnic backgrounds and genotypic qualities. Our study clearly demonstrates that encrypted genomic data can be used for data sharing without loss of information or data sharing barrier. Author SummaryEstimating pairwise genetic relatedness within a single cohort is straightforward. However, in practice, related samples are often distributed across different cohorts, making it challenging to estimate inter-cohort relatedness. In this study, we propose a method called encrypted genotype regression (encG-reg), which provides an unbiased estimation of inter-cohort relatedness using encrypted genotypes. The genotype matrix of each cohort is masked by a random matrix, which acts similarly to a private key in a cryptographic scheme. This masking process produces encrypted genotypes, which are a projection of the original genotype matrix. We derive the expectation and particularly the sampling variance for encG-reg, the latter involves eighth-order moments calculation. encG-reg allows us to accurately identify relatedness across cohorts, even for large-scale biobank data. To demonstrate the efficacy of encG-reg, we verified it in a multi-ethnicity UK Biobank dataset comprising 485,158 samples. For this case, we successfully tracked down to the 1st-degree relatedness (such as full sibs and parent-offspring). Furthermore, we used encG-reg in a collaboration involving 9 Chinese cohorts, encompassing a total of 54,092 samples from 5 genomic centers. It is worth noting that if the number of effective markers is sufficient encG-reg has the potential to detect even more distant degrees of relatedness beyond what we demonstrated.

genetics↗

bioRxiv2022

Determinants and Mechanisms of the Low Fusogenicity and Endosomal Entry of Omicron Subvariants

The rapid spread and strong immune evasion of the SARS-CoV-2 Omicron subvariants has raised serious concerns for the global COVID-19 pandemic. These new variants exhibit reduced fusogenicity and increased endosomal entry pathway utilization compared to the ancestral D614G variant, the underlying mechanisms of which remain elusive. Here we show that the C-terminal S1 mutations of the BA.1.1 subvariant, H655Y and T547K, critically govern the low fusogenicity of Omicron. Notably, H655Y also dictates the enhanced endosome entry pathway utilization. Mechanistically, T547K and H655Y likely stabilize the spike trimer conformation, as shown by increased molecular interactions in structural modeling as well as reduced S1 shedding. Importantly, the H655Y mutation also determines the low fusogenicity and high dependence on the endosomal entry pathway of other Omicron subvariants, including BA.2, BA.2.12.1, BA.4/5 and BA.2.75. These results uncover mechanisms governing Omicron subvariant entry and provide insights into altered Omicron tissue tropism and pathogenesis.

microbiology↗

bioRxiv2022

Landscape of semi-extractable RNAs across five human cell lines

Phase-separated membraneless organelles often contain RNAs that exhibit unusual semi-extractability upon the conventional RNA extraction method, and can be efficiently retrieved by needle shearing or heating during RNA extraction. Semi-extractable RNAs are promising resources for understanding RNA-centric phase separation. However, limited assessments have been performed to systematically identify and characterize semi-extractable RNAs. In this study, 1,074 semi-extractable RNAs were identified across five human cell lines, including ASAP1, DANT2, EXT1, FTX, IGF1R, LIMS1, NEAT1, PHF21A, PVT1, SCMH1, STRG.3024.1, TBL1X, TCF7L2, TVP23C-CDRT4, UBE2E2, ZCCHC7, ZFAND3, and ZSWIM6, which exhibited consistent semi-extractability. By integrating publicly available datasets, we found that semi-extractable RNAs tend to be distributed in the nuclear compartments but are dissociated from the chromatin. Long and repeat-containing semi-extractable RNAs act as hubs to provide global RNA-RNA interactions. Semi-extractable RNAs were divided into four groups based on their k-mer content. The NEAT1 group preferred to interact with paraspeckle proteins, such as FUS and NONO, implying that RNAs in this group are potential candidates of architectural RNAs that constitute nuclear bodies.

bioinformatics↗