Biology subjects

Yang, J.-H.

Publications and source records attributed to Yang, J.-H..

18 recordsLinked to original sources

bioRxiv2026

Reduced LANCL1-AS1 in old human skeletal muscle diminishes mitochondrial activity, shortens mt-mRNA poly(A) tails, and suppresses myogenesis

Regeneration of skeletal muscle preserves muscle mass and function, which decline with age. Here, we sought to identify long noncoding (lnc)RNAs involved in skeletal muscle myogenesis and potentially relevant to muscle aging. Cross-sectional analysis of skeletal muscle transcriptomes from healthy 22-through 89-year-old individuals revealed lncRNA LANCL1-AS1 among the top declining transcripts. Conversely, LANCL1-AS1 increased robustly during skeletal myogenesis and promoted myogenic differentiation in culture. Affinity pulldown by ChIRP followed by mass spectrometry revealed that LANCL1-AS1 associated with the mitochondrial protein LRPPRC, enhancing the formation of the chaperone complex LRPPRC-SLIRP, which maintains longer poly(A) tails of mitochondrial (mt-)mRNAs and stabilizes mt-mRNAs. Importantly, while myoblasts from old rhesus monkey muscle expressed lower levels of LANCL1-AS1 and mt-mRNAs, and displayed lower mitochondrial activity than young monkey myoblasts, overexpressing LANCL1-AS1 in old myoblasts restored mitochondrial activity and myogenesis. We propose that the age-associated reduction in LANCL1-AS1 contributes to impaired mitochondrial function and reduced myogenic capacity in aging skeletal muscle.

molecular biology↗

bioRxiv2026

dbGIST: An LLM-Assisted Multi-Omics Resource for Target Exploration and Cross-Dataset Validation in Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, yet GIST-specific omics evidence remains scattered across small cohorts and is not represented as a dedicated disease project in major cancer genomics resources, limiting reproducible target exploration. Here, we present dbGIST (https://www.dbgist.com), a dedicated GIST-focused multi-omics resource built to make dispersed GIST evidence searchable, analyzable, and reusable. dbGIST harmonizes data from 37 centers and 1,991 samples, including pathologically verified in-house cohorts, across genomics, bulk transcriptomics, proteomics, phosphoproteomics, and single-cell transcriptomics, and couples these data with curated clinical annotations covering survival, mutation status, risk stratification, metastasis or recurrence, mitotic index, tumor site and size, and imatinib response. The platform supports cohort-level molecular-clinical association, survival, enrichment, immune-infiltration, drug-sensitivity, and single-cell analyses through interactive visualizations, downloadable source data, and public APIs for programmatic access to reusable analysis outputs and visualization-ready data. An optional LLM-assisted interface helps users navigate analyses and interpret outputs. Using MCM7 as a case study, dbGIST linked a resource-derived candidate to survival, risk features, metastatic or recurrent disease, imatinib-response phenotypes, proliferative cell states, and in vitro GIST-cell behavior. dbGIST therefore provides a traceable and interoperable resource for target exploration and precision oncology research in GIST.

cancer biology↗

bioRxiv2026

SenCat: Cataloging human cell senescence through multiomic profiling of multiple senescent primary cell types

There is an urgent need to comprehensively catalog senescence markers across cell types in an organism in order to characterize senotypes and senescent cell heterogeneity. Here, we profiled the transcriptomes and proteomes in 14 different primary human cell types undergoing over 30 senescence paradigms to create a senescence catalog we termed SenCat. We found that, while senescent cells from all primary tissue types did not share a single unique marker, they did activate shared specific metabolic and damage-response pathways implicated in tissue repair. Machine learning analysis of the SenCat transcriptomic and proteomic datasets successfully identified independent sets of senescent human cells, and senescent-like cells in mouse lung and kidney. In sum, SenCat represents a much-needed resource to identify senescent cells across tissues in the body. HIGHLIGHTSO_LIIdentifying senescent cells in organisms in vivo remains a challenge C_LIO_LIWe created SenCat: a catalog transcriptomes and proteomes of senescent primary cells C_LIO_LIMachine learning (ML) analysis of SenCat identified robust senescence scores C_LIO_LIML-derived senescence scores uncovered senescent-like cell dynamics in vivo C_LI

molecular biology↗

bioRxiv2024

The Taiwan Precision Medicine Initiative: A Cohort for Large-Scale Studies

The Taiwan Precision Medicine Initiative (TPMI), a project initiated by the Academia Sinica in collaboration with 16 major medical centers around Taiwan, has recruited 565,390 participants who consented to provide DNA samples for genetic profiling and grant access to their electronic medical records (EMR) for studies to develop precision medicine. Access to the EMR is both retrospective and prospective, allowing researchers to conduct prospective studies over time. Genetic profiling is done with population-optimized SNP arrays for the Han Chinese populations that enable genetic analyses such as genome-wide association, phenome-wide association, and polygenic risk score studies to evaluate common disease risk and pharmacogenetic response. Furthermore, the TPMI participants agree to be contacted for future research opportunities related to their genetic risks and receive personalized genetic risk profiles with health management recommendations. TPMI has established the TPMI Data Access Platform (TDAP), a central database and analysis platform that both safeguards the security of the data and facilitates academic research. The TPMI is the largest non-European cohort that merges genetic profiles with EMR in the world. With a cohort that can be followed over time, it can be utilized to validate genetic risk prediction models, conduct clinical trials to show the efficacy of risk-based health management, and optimize health policies based on genetic risks. In this report, we describe the TPMI study design, the population and genetic characteristics of the TPMI cohort, and the power it provides to conduct crucial studies in developing precision medicine on a population and personal level. As Han Chinese represent almost 20% of the worlds population, the results of TPMI studies will benefit >1.4 billion people around the world and serve as a model for developing population-based precision medicine.

genetics↗

bioRxiv2024

Neural Circuit Revision in Retinal Remodeling, A Pathoconnectomics Approach

Retinitis pigmentosa (RP), a retinal degenerative disease, is characterized by progressive photoreceptor loss and ongoing remodeling and rewiring of the inner retina. This study investigates rod network rewiring through pathoconnectomic evaluation and its impacts on signaling patterns. The glycinergic Aii amacrine cell (Aii) plays a central role in the healthy retina bridging rod and cone pathways, enabling an increased dynamic range of vision. Pathoconnectomics reveals altered connectivity in both the excitatory drive and gap junctional coupling of Aiis in retinal degeneration. A computational model of the rewired network was developed to assess the functional consequences of these structural changes by simulating light-evoked responses and changes in excitatory postsynaptic potentials (EPSPs). The model predicts significant changes in bipolar and Aii EPSPs between active and baseline conditions, driven by newly formed gap junctions in the degenerate retina. Notably, the aberrant circuitry induces rhythmic firing of up to 10 Hz in retinal ganglion cells, consistent with network depolarization relative to the healthy baseline state. These findings align with patch-clamp observations in rd1 and rd10 mouse models of RP, suggesting that Aii-mediated network alterations may underlie early clinical symptoms, including impaired adaptation between photopic and scotopic vision. More broadly, this work demonstrates that integrating computational modeling with pathoconnectomics enables predictive analysis of signaling in early-stage retinal degeneration and may help identify windows for therapeutic intervention. Such models could be further extended with multi-scale bioelectromagnetic simulations to optimize neurostimulation strategies aimed at slowing disease progression. Author summaryUnderstanding how retinal degeneration alters wiring topologies of the inner retina is important for the success of multiple therapeutic interventions, including cell replacement strategies, optogenetics, and electrode implants. Here, we continue our evaluation of retinal pathoconnectome 1 (RPC1), describing additional network-level changes occurring early in retinal degeneration. This analysis extends our previous findings on the emergence of gap junctions in rod bipolar cells in retinal degeneration to include the effects of these changes on the synaptic strength of inputs to the Aii. We then model how these network changes overall effect retinal processing through the creation of a more complete degenerate retina model. From these results we propose the emergence of aberrant gap junctions in the rod pathway as the network cause of atypical retinal ganglion cell firing and provide the field with a realistic network model for evaluating and optimizing therapeutic strategies.

neuroscience↗

bioRxiv2022

Structural and biophysical properties of FopA, a major outer membrane protein of Francisella tularensis

Francisella tularensis is an extremely infectious pathogen and a category A bioterrorism agent. It causes the highly contagious zoonosis, Tularemia. Currently, FDA approved vaccines against tularemia are unavailable. F. tularensis outer membrane protein A (FopA) is a well-studied virulence determinant and protective antigen against tularemia. It is a major outer membrane protein (Omp) of F. tularensis. However, FopA-based therapeutic intervention is hindered due to lack of complete structural information for membrane localized mature FopA. In our study, we established recombinant expression, monodisperse purification, crystallization and X-ray diffraction ([~]6.5 [A]) of membrane localized mature FopA. Further, we performed bioinformatics and biophysical experiments to unveil its structural organization in the outer membrane. FopA consists of 393 amino acids and has less than 40% sequence identity to known bacterial Omps. Using comprehensive sequence alignments and structure predictions together with existing partial structural information, we propose a two-domain organization for FopA. Circular dichroism spectroscopy and heat modifiability assay confirmed FopA has a {beta}-barrel domain consistent with alphafold2s prediction of an eight stranded {beta}-barrel at the N-terminus. Small angle X-ray scattering (SAXS) and native-polyacrylamide gel electrophoresis revealed FopA purified in detergent micelles is predominantly dimeric. Molecular density derived from SAXS at 31 [A] shows putative dimeric N-terminal {beta}-barrels surrounded by detergent corona and connected to C-terminal domains via flexible linker. Disorder analysis predicts N- and C-terminal domains are interspersed by a long intrinsically disordered region and alphafold2 predicts this region to be largely unstructured. Taken together, we propose a dimeric, two-domain organization of FopA in the outer membrane: the N-terminal {beta}-barrel is membrane embedded, provides dimerization interface and tethers to membrane extrinsic C-terminal domain via long flexible linker. Structure determination of membrane localized mature FopA is essential to understand its role in pathogenesis and develop anti-tularemia therapeutics. Our results pave the way towards it.

biochemistry↗

bioRxiv2021

Revision of the genus Dichaetophora Duda (Diptera: Drosophilidae), part I: DNA bar-coding and molecular phylogenetic reconstruction

The genus Dichaetophora is currently comprised of 67 formally described species assigned into five species groups, i.e., agbo, tenuicauda, acutissima, sinensis and trilobita. In the present study, we challenged to delimit species from a huge amount of samples of Dichaetophora and allied taxa (the genus Mulgravea and the subgenus Dudaica of Drosophila) collected from a wide range of the Oriental and east Palearctic regions. We first sorted all specimens into morpho-species, which were tentatively classified into the species groups of Dichaetophora, Mulgravea and Dudaica based on the morphological diagnoses for these supraspecific taxa. Then, we selected representative specimen(s) for each morpho-species and subjected them to barcoding of COI (the cytochrome c oxidase subunit I gene) sequences. The applied ABGD (automatic barcode gap discovery) algorithm estimated a total of 222 MOTUs (molecular operational taxonomic units). Although most of the morpho-species were recognized as individual MOTUs, some others were divided into multiple MOTUs or combined into a single MOTU, suggesting the existence of cryptic sibling species, subspecies or intraspecific genetic varieties. Out of the 222 MOTUs, 88 representing the supraspecific taxa of Dichaetophora, Mulgravea and Dudaica were selected, along with 33 species from major genera and subgenera of Drosophila in the tribe Drosophilini, as in-group (four species from the tribe Colocasiomyini as out-group) for phylogenetic reconstruction. We analyzed a dataset of concatenated nucleotide sequences of 12 nuclear gene markers by the maximum likelihood and Bayesian inference methods. As a result, the three focal taxa (i.e., Dichaetophora, Mulgravea and Dudaica) formed a clade, which we called the "pan-Dichaetophora". Within this large clade, the agbo, tenuicauda, sinensis and trilobita groups of Dichaetophora, Mulgravea and Dudaica were recovered as monophyletic groups, but Dichaetophora and its acutissima group were regarded as paraphyletic. In addition, two clusters were recognized among ungrouped MOTUs of Dichaetophora. Thus, the present study has uncovered some problems in the taxonomy of the pan-Dichaetophora. Solving such problems will be challenged in Part II of this serial work.

zoology↗

bioRxiv2020

Direct Observation of the Mechanism of Antibiotic Resistance by Mix-and-Inject at the European XFEL

In this study, we follow the diffusion and buildup of occupancy of the substrate ceftriaxone in M. tuberculosis {beta}-lactamase BlaC microcrystals by structural analysis of the enzyme substrate complex at single millisecond time resolution. We also show the binding and the reaction of an inhibitor, sulbactam, on a slower millisecond time scale. We use the mix-and-inject technique to initiate these reactions by diffusion, and determine the resulting structures by serial crystallography using ultrafast, intense X-ray pulses from the European XFEL (EuXFEL) arriving at MHz repetition rates. Here, we show how to use the EuXFEL pulse structure to dramatically increase the size of the data set and thereby the quality and time resolution of "molecular movies" which unravel ligand binding and enzymatically catalyzed reactions. This shows the great potential for the EuXFEL as a tool for biomedically relevant research, particularly, as shown here, for investigating bacterial antibiotic resistance. One Sentence SummaryDirect observation of fast ligand binding in a biomedically relevant enzyme at near atomic resolution with MHz X-ray pulses at the European XFEL.

biophysics↗

bioRxiv2020

CREB1 contributes colorectal cancer cell plasticity by regulating lncRNA CCAT1 and NF-κB pathways

The CREB1 gene encodes a pleiotropic transcription factor that frequently dysregulated in cancers. CREB1 can regulates tumour cell status of proliferation or migration, however, the molecular basis for this switch involvement in cell plasticity has not been fully understood. Here, we show that knocking out CREB1 triggered a remarkable effect of epithelial-mesenchymal transition (EMT) and led to the occurrence of inhibited proliferation and enhanced motility in cancer cells. Mechanistically, CREB1-knockout cells showed arrest in the G0/G1 phase as a result of impaired CREB1-dependent transcription of CCAT1 and E2F1. Interestingly, the competition between the coactivator CBP/p300 for CREB1 and p65 leads to the activation of the NF-{kappa}B pathway in cells with CREB1 disrupted, which induces an EMT phenotype and enhances motility. These studies identified previously unknown mechanisms of CREB1 in cell plasticity via its lncRNA and protein effector pathways, revealing an important feature that should be considered in CREB1-targeted tumour therapies.

cell biology↗

bioRxiv2020

A Pathoconnectome of Early Neurodegeneration

Connectomics has demonstrated that synaptic networks and their topologies are precise and directly correlate with physiology and behavior. The next extension of connectomics is pathoconnectomics: to map neural network synaptology and circuit topologies corrupted by neurological disease in order to identify robust targets for therapeutics. In this report, we characterize the first pathoconnectome, in this case, generated from a retina with photoreceptor degeneration. We observe aberrant connectivity in the rod-network pathway and novel synaptic connections deriving from neurite sprouting. These observations reveal principles of neuron responses to the loss of network components and can be extended to other neurodegenerative diseases.

neuroscience↗

bioRxiv2019

DNA Break-Induced Epigenetic Drift as a Cause of Mammalian Aging

There are numerous hallmarks of aging in mammals, but no unifying cause has been identified. In budding yeast, aging is associated with a loss of epigenetic information that occurs in response to genome instability, particularly DNA double-strand breaks (DSBs). Mammals also undergo predictable epigenetic changes with age, including alterations to DNA methylation patterns that serve as epigenetic \"age\" clocks, but what drives these changes is not known. Using a transgenic mouse system called \"ICE\" (for inducible changes to the epigenome), we show that a tissues response to non-mutagenic DSBs reorganizes the epigenome and accelerates physiological, cognitive, and molecular changes normally seen in older mice, including advancement of the epigenetic clock. These findings implicate DSB-induced epigenetic drift as a conserved cause of aging from yeast to mammals.\n\nOne Sentence SummaryDNA breaks induce epigenomic changes that accelerate the aging clock in mammals

molecular biology↗

bioRxiv2019

Erosion of the Epigenetic Landscape and Loss of Cellular Identity as a Cause of Aging in Mammals

All living things experience entropy, manifested as a loss of inherited genetic and epigenetic information over time. As budding yeast cells age, epigenetic changes result in a loss of cell identity and sterility, both hallmarks of yeast aging. In mammals, epigenetic information is also lost over time, but what causes it to be lost and whether it is a cause or a consequence of aging is not known. Here we show that the transient induction of genomic instability, in the form of a low number of non-mutagenic DNA breaks, accelerates many of the chromatin and tissue changes seen during aging, including the erosion of the epigenetic landscape, a loss of cellular identity, advancement of the DNA methylation clock and cellular senescence. These data support a model in which a loss of epigenetic information is a cause of aging in mammals.\n\nOne Sentence SummaryThe act of repairing DNA breaks induces chromatin reorganization and a loss of cell identity that may contribute to mammalian aging

molecular biology↗

bioRxiv2019

Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming

Ageing is a degenerative process leading to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise, which disrupts youthful gene expression patterns that are required for cells to function optimally and recover from damage1-3. Changes to DNA methylation patterns over time form the basis of an ageing clock4, 5, but whether old individuals retain information to reset the clock and, if so, whether this would improve tissue function is not known. Of all the tissues in the body, the central nervous system (CNS) is one of the first to lose regenerative capacity6, 7. Using the eye as a model tissue, we show that expression of Oct4, Sox2, and Klf4 genes (OSK) in mice resets youthful gene expression patterns and the DNA methylation age of retinal ganglion cells, promotes axon regeneration after optic nerve crush injury, and restores vision in a mouse model of glaucoma and in normal old mice. This process, which we call recovery of information via epigenetic reprogramming or REVIVER, requires the DNA demethylases Tet1 and Tet2, indicating that DNA methylation patterns dont just indicate age, they participate in ageing. Thus, old tissues retain a faithful record of youthful epigenetic information that can be accessed for functional age reversal.

molecular biology↗

bioRxiv2018

Association of Prevotella enterotype with polysomnographic data in obstructive sleep apnea/hypopnea syndrome patients

Intermittent hypoxia and sleep fragmentation are critical pathophysiological processes involved in obstructive sleep apnea/hypopnea syndrome (OSAHS). These manifestation independently affect similar brain regions and contribute to OSAHS-related comorbidities that are known to be related to the host gut alteration microbiota. We hypothesized that microbiota disruption influences the pathophysiological processes of OSAHS through a microbiota-gut-brain axis. Thus, we aim to survey enterotypes and polysomnographic data of OSAHS patients. Subjects were diagnosed by polysomnography, from whom fecal samples were obtained and analyzed for the microbiome composition by variable regions 3-4 of 16S rRNA pyrosequencing and bioinformatic analyses. We examined blood cytokines level of all subjects. Three enterotypes Bacteroides (n=73), Ruminococcus (n=14), and Prevotella (n=26) were identified. Central apnea indices, mixed apnea indices, N1 sleep stage, mean apnea-hypopnea duration, and arousal indices were increased in apnea-hypopnea indices (AHI) [≥]15 patients with the Prevotella enterotype. However, for AHI<15 subjects, obstructive apnea indices and systolic blood pressure were significantly observed in Ruminococcus and Prevotella enterotypes, respectively. The present study indicates the possibility of pathophysiological interplay between enterotypes and sleep structure disruption in sleep apnea through a microbiota-gut-brain axis and offers some new insight toward the pathogenesis of OSAHS.\n\nImportanceIntermittent hypoxia (IH) and sleep fragmentation (SF) are hallmarks of are the predominant mechanism underlying obstructive sleep apnea/hypopnea syndrome (OSAHS). Moreover, IH and SF of pathophysiological roles in the gut microbiota dysbiosis in OSAHS have been demonstrated. We hypothesized that gut microbiota disruption may cross-talk the brain function via microbiota-gut-brain axis. Indeed, we observed central apnea indices and other parameters of disturbances during sleep were significantly elevated in AHI[≥]15 patients with the Prevotella enterotype. This enterotype prone to endotoxin production, driving systemic inflammation, ultimately contributes to OSAHS-linked comorbidities. Vice versa, increasing the arousal index leads to systemic inflammatory changes and accompanies metabolic dysfunction. We highlight that the possibility that the microbiota-gut-brain axis operates a bidirectional effect on the development of OSAHS pathology.

microbiology↗

bioRxiv2018

Widespread and polymorphous noncoding amino acid residues in human sperm proteome

Proteins are usually deciphered by translation of the coding genome; however, their amino acid residues are seldom determined directly across the proteome. Herein, we describe a systematic workflow for identifying all possible protein residues that differ from the coding genome, termed noncoded amino acids (ncAAs). By measuring the mass differences between the coding amino acids and the actual protein residues in human spermatozoa, over a million nonzero delta masses were detected, fallen into 424 high-quality Gaussian clusters and 571 high-confidence ncAAs spanning 29,053 protein sites. Most ncAAs are novel with unresolved side-chains and discriminative between healthy individuals and patients with oligoasthenospermia. For validation, 40 out of 98 ncAAs that matched with amino acid substitutions were confirmed by exon sequencing. This workflow revealed the widespread existence of previously unreported ncAAs in the sperm proteome, which represents a new dimension on the understanding of amino acid polymorphisms at the proteomic level.\n\nHighlightsO_LI571 ncAAs spanning 108,000 protein sites were identified in human sperm proteome.\nC_LIO_LIMost ncAAs are novel with unresolved sidechains and found at unreported protein sites.\nC_LIO_LIExon sequencing confirmed 40 of 98 ncAAs that matched with amino acid substitutions.\nC_LIO_LIMany ncAAs are linked with disease and have potential for diagnosis and targeting.\nC_LI\n\neTOC BlurbWe describe a systematic identification of all possible protein residues that were not encoded by their genomic sequences. A total of 571 high-confidence most novel noncoded amino acids were identified in human sperm proteome, corresponding to over 108,000 ncAA-containing protein sites. For validation, 40 out of 98 ncAAs that matched to amino acid substitutions were confirmed by exon sequencing. These ncAAs are discriminative between individuals and expand our understanding of amino acid polymorphisms in human proteomes and diseases.

molecular biology↗

bioRxiv2018

Variability and compensation of cardiomycoyte ionic conductances at the population level

Conductances of ion channels and transporters controlling cardiac excitation may vary in a population of subjects with different cardiac gene expression patterns. However, the amount of variability and its origin are not quantitatively known. We propose a new computational method to predict this variability that consists of finding combinations of conductances generating a normal intracellular Ca2+ transient without any constraint on the action potential. Furthermore, we validate experimentally its predictions using the Hybrid Mouse Diversity Panel, a model system of genetically diverse mouse strains that allows us to quantify inter-subject versus intra-subject variability. The method predicts that conductances of inward Ca2+ and outward K+ currents compensate each other to generate a normal Ca2+ transient in good quantitative agreement with current measurements in ventricular myocytes from hearts of different isogenic strains. Our results suggest that a feedback mechanism sensing the aggregate Ca2+ transient of the heart suffices to regulate ionic conductances.

biophysics↗

bioRxiv2018

MicroRNA-122 supports robust innate immunity in hepatocytes by suppressing STAT3 phosphorylation

The intrinsic innate immunity of hepatocytes is essential for the control of hepatitis viruses and influences the outcome of antiviral therapy. MicroRNA-122 (miR-122) is the most abundant microRNA in hepatocytes and is a central player in liver biology and disease. However, little is known about the role of miR-122 in hepatocyte innate immunity. Herein, we show that restoring miR-122 levels in hepatoma cells markedly increased the activation of both type III and type I interferons (IFNs) in response to hepatitis C virus (HCV) RNA or poly(I:C). We determined that miR-122 promotes IFN production through down-regulating the tyrosine (Tyr705) phosphorylation of STAT3. We show that STAT3 represses IFN activation by inhibiting interferon regulatory factor 1 (IRF1), which is rate-limiting for maximal IFN expression, especially type III IFNs. Through large-scale screening, we identified that miR-122 targets MERTK, FGFR1 and IGF1R, three oncogenic receptor tyrosine kinases that directly promote STAT3 phosphorylation. These findings reveal a previously unknown role for miR-122 in hepatic immunity and indicate a new potential strategy for treating hepatic infections through targeting STAT3.

molecular biology↗

bioRxiv2017

Discovering the Interactions between Circular RNAs and RNA-binding Proteins from CLIP-seq Data using circScan

Although tens of thousands of circular RNAs (circRNAs) have been identified in mammalian genomes, only few of them have been characterized with biological functions. Here, we report a new approach, circScan, to identify regulatory interactions between circRNAs and RNA-binding proteins (RBPs) by discovering back-splicing reads from Cross-Linking and Immunoprecipitation followed by high-throughput sequencing (CLIP-seq) data. By using our method, we have systematically scanned ~1500 CLIP-seq datasets, and identified ~12540 and ~1090 novel circRNA-RBP interactions in human and mouse genomes, respectively, which include all known interactions between circRNAs and Argonaute (AGO) proteins. More than twenty novel interactions were further experimentally confirmed by RNA Immunoprecipitation quantitative PCR (RIP-qPCR). Importantly, we uncovered that some natural circRNAs interacted with cap-independent translation factors eukaryotic initiation factor 3 (eIF3) and N6-Methyladenosine (m6A), indicating they can be translated into proteins. These findings demonstrate that circRNAs are regulated by various RBPs, suggesting they may play important roles in diverse biological processes.

molecular biology↗