Biology subjects

Hu, Y.

Publications and source records attributed to Hu, Y..

At least 451 records · Page 25Linked to original sources

bioRxiv2021

Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617

COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identified two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generated a bispecific antibody. Lead antibodies showed strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solved several cryo-EM structures at [~]3 [A] resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and revealed distinct epitopes, binding patterns, and conformations. The lead clones also showed potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generated and characterized a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.

immunology↗

bioRxiv2021

An expanded toolkit for Drosophila gene tagging using synthesized homology donor constructs for CRISPR mediated homologous recombination

Previously, we described a large collection of Drosophila strains that each carry an artificial exon containing a T2AGAL4 cassette inserted in an intron of a target gene based on CRISPR-mediated homologous recombination (Lee et al., 2018). These alleles permit numerous applications and have proven to be very useful. Initially, the homologous recombination-based donor constructs had long homology arms (>500 bps) to promote precise integration of large constructs (>5kb). Recently, we showed that in vivo linearization of the donor constructs enables insertion of large artificial exons in introns using short homology arms (100-200 bps) (Kanca et al., 2019a). Shorter homology arms make it feasible to commercially synthesize homology donors and minimize the cloning steps for donor construct generation. Unfortunately, about 50% of Drosophila genes lack suitable coding introns for integration of artificial exons. Here, we report the development of new set of constructs that allow the replacement of the coding region of genes that lack suitable introns with a KozakGAL4 cassette, generating a knock-out/knock-in allele that expresses GAL4 similarly as the targeted gene. We also developed custom vector backbones to further facilitate and improve transgenesis. Synthesis of homology donor constructs in custom plasmid backbones that contain the target gene sgRNA obviates the need to inject a separate sgRNA plasmid and significantly increases the transgenesis efficiency. These upgrades will enable the targeting of nearly every fly gene, regardless of exon-intron structure, with a 70-80% success rate.

genetics↗

bioRxiv2021

Computational Mapping of the Human-SARS-CoV-2 Protein-RNA Interactome

Strong evidence suggests that human human RNA-binding proteins (RBPs) are critical factors for viral infection, yet there is no feasible experimental approach to map exact binding sites of RBPs across the SARS-CoV-2 genome systematically at a large scale. We investigated the role of RBPs in the context of SARS-CoV-2 by constructing the first in silico map of human RBP / viral RNA interactions at nucleotide-resolution using two deep learning methods (pysster and DeepRiPe) trained on data from CLIP-seq experiments. We evaluated conservation of RBP binding between 6 other human pathogenic coronaviruses and identified sites of conserved and differential binding in the UTRs of SARS-CoV-1, SARS-CoV-2 and MERS. We scored the impact of variants from 11 viral strains on protein-RNA interaction, identifying a set of gain-and loss of binding events. Lastly, we linked RBPs to functional data and OMICs from other studies, and identified MBNL1, FTO and FXR2 as potential clinical biomarkers. Our results contribute towards a deeper understanding of how viruses hijack host cellular pathways and are available through a comprehensive online resource (https://sc2rbpmap.helmholtz-muenchen.de).

bioinformatics↗

bioRxiv2021

Theta oscillations in the prefrontal-hippocampal circuit do not couple to respiration-related oscillations

Oscillatory activity is thought to coordinate neural computations across brain regions, and theta oscillations are critical for learning and memory. Because the frequency of respiratory-related oscillations (RROs) in rodents can overlap with the frequency of theta in the prefrontal cortex (PFC) and the hippocampus, we asked whether odor-cued working memory may be supported by coupling between these two oscillations. We first confirmed that RROs are propagated to the hippocampus and PFC and that RRO frequency overlaps with canonical theta frequency. However, we found low coherence between RROs and local theta oscillations in the hippocampus-PFC network when the two types of oscillations overlapped in frequency. This effect was observed during all behavioral phases including during movement and while odors were actively sampled when stationary. Despite the similarity in frequency, RROs and theta oscillations therefore appear to be limited to supporting computation in distinct networks, which suggests that sustained long-range coordination between oscillation patterns that depend on separate pacemakers is not necessary to support at least one type of working memory.

neuroscience↗

bioRxiv2021

REPTOR/CREBRF encode key regulators of muscle energy metabolism

Metabolic flexibility of muscle tissue describes the capacity to use glucose or lipids as energy substrates and its disruption is associated with metabolic dysfunction. Cancer-induced cachexia is a metabolic syndrome linked with muscle wasting, changes in muscle energy metabolism and lower life expectancy in cancer patients. The molecular mechanisms driving metabolic changes in muscle, however, are poorly characterized. Here, using a Drosophila model of systemic metabolic dysfunction triggered by yorkie-induced gut tumors, we identify the transcription factor REPTOR as a key regulator of energy metabolism in muscle. We show that REPTOR is upregulated in muscles of adult flies with gut yorkie-tumors, where it is necessary to modulate glucose metabolism. REPTOR expression in muscles is induced by ImpL2, a tumor-derived insulin binding protein that reduces systemic insulin signaling, or by nutritional restriction. Further, in vitro and in vivo studies indicate that high activity of REPTOR is sufficient to increase glucose content, transcriptionally repress phosphofructokinase and increase mitochondrial respiration. Consistent with the fly studies, higher levels of CREBRF, the mammalian ortholog of REPTOR, reduce glycolysis in mouse myotubes while promoting an oxidative phenotype. Altogether, our results implicate REPTOR/CREBRF as key regulators of muscle metabolism and metabolic flexibility that share a conserved function as repressors of glycolysis and promoters of oxidative phosphorylation.

physiology↗

bioRxiv2021

SMAD4 and TGFβ are architects of inverse genetic programs during fate-determination of antiviral memory CD8 T cells

Transforming growth factor {beta} (TGF{beta}) is a morphogenic protein that augments antiviral immunity by altering the functional properties of pathogen-specific memory CD8 T cells. During infection TGF{beta} inhibits formation of effector (TEFF) and central memory CD8 T cells (TCM), while encouraging tissue-resident memory CD8 T cells (TRM) to settle in peripheral tissues. SMAD proteins are signaling intermediates that are used by members of the TGF cytokine family to modify gene expression. For this study, RNA-sequencing was used to explore how regulation via SMAD4 alters the transcriptional profile of antiviral CTLs during infection. We show that SMAD4 and TGF{beta} cooperatively regulate a collection of genes that determine whether specialized populations of pathogen-specific CTLs circulate around the body, or settle in peripheral tissue. The target genes include multiple homing receptors (CD103, KLRG1 and CD62L) and transcription factors (Hobit and EOMES) that support memory formation. While TGF{beta} uses a canonical SMAD-dependent signaling pathway to induce CD103 expression on TRM cells, an alternative SMAD4-dependent mechanism is required for formation of TEFF and TCM cells in the circulation. Graphical abstractTGF{beta} and SMAD4 modulate gene expression in reciprocal directions during differentiation of antiviral CTLs. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/472993v2_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@5ac140org.highwire.dtl.DTLVardef@455a2aorg.highwire.dtl.DTLVardef@1227d96org.highwire.dtl.DTLVardef@16336b9_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2021

Subfamily-specific differential contribution of individual monomers and the tether sequence to mouse L1 promoter activity

BackgroundThe internal promoter in L1 5UTR is critical for autonomous L1 transcription and initiating retrotransposition. Unlike the human genome, which features one contemporarily active subfamily, four subfamilies (A_I, Gf_I and Tf_I/II) have been amplifying in the mouse genome in the last one million years. Moreover, mouse L1 5UTRs are organized into tandem repeats called monomers, which are separated from ORF1 by a tether domain. In this study, we aim to compare promoter activities across young mouse L1 subfamilies and investigate the contribution of individual monomers and the tether sequence. ResultsWe observed an inverse relationship between subfamily age and the average number of monomers among evolutionarily young mouse L1 subfamilies. The youngest subgroup (A_I and Tf_I/II) on average carry 3-4 monomers in the 5UTR. Using a single-vector dual-luciferase reporter assay, we compared promoter activities across six L1 subfamilies (A_I/II, Gf_I and Tf_I/II/III) and established their antisense promoter activities in a mouse embryonic fibroblast cell line. Using consensus promoter sequences for three subfamilies (A_I, Gf_I and Tf_I), we dissected the differential roles of individual monomers and the tether domain in L1 promoter activity. We validated that, across multiple subfamilies, the second monomer consistently enhances the overall promoter activity. For individual promoter components, monomer 2 is consistently more active than the corresponding monomer 1 and/or the tether for each subfamily. Importantly, we revealed intricate interactions between monomer 2, monomer 1 and tether domains in a subfamily-specific manner. Furthermore, using three-monomer 5UTRs, we established a complex nonlinear relationship between the length of the outmost monomer and the overall promoter activity. ConclusionsThe laboratory mouse is an important mammalian model system for human diseases as well as L1 biology. Our study extends previous findings and represents an important step toward a better understanding of the molecular mechanism controlling mouse L1 transcription as well as L1s impact on development and disease.

genomics↗

bioRxiv2021

The Atypical Antipsychotic Quetiapine Induces Multiple Antibiotic Resistance in Escherichia coli

Atypical antipsychotic (AAP) medication is a critical tool for treating symptoms of psychiatric disorders. While AAPs primarily target dopamine (D2) and serotonin (5HT2A and 5HT1A) receptors, they also exhibit intrinsic antimicrobial activity as an off-target effect. Because AAPs are often prescribed to patients for many years, a potential risk associated with long-term AAP use is the unintended emergence of bacteria with antimicrobial resistance (AMR). Here, we show that exposure to the AAP quetiapine at estimated gut concentrations promotes AMR in Escherichia coli after six weeks. Quetiapine-exposed isolates exhibited an increase in minimal inhibitory concentrations (MICs) for ampicillin, tetracycline, ceftriaxone, and levofloxacin. By whole genome sequencing analysis, we identified mutations in genes that confer AMR, including the repressor for the multiple antibiotic resistance mar operon (marR), and real-time RT-qPCR analysis showed increased levels of marA, acrA, and tolC mRNAs and a reduced level of ompF mRNA in the isolates carrying marR mutations. To determine the contribution of each marR mutation to AMR, we constructed isogenic strains carrying individual mutant marR alleles in the parent background and re-evaluated their resistant phenotypes using MIC and RT-qPCR assays. While marR mutations induced a robust activity of the mar operon, they resulted in only a modest increase in MICs. Interestingly, although these marR mutations did not fully recapitulate the AMR phenotype of the quetiapine-exposed isolates, we show that marR mutations promote growth fitness in the presence of quetiapine. Our findings revealed an important link between the use of AAPs and AMR development in E. coli.

microbiology↗

bioRxiv2021

Three heads are better than one: Cooperative learning brains wire together when a consensus is reached

Theories of human learning converge on the view that individuals working together learn better than do those working alone. Little is known, however, about the neural mechanisms of learning through cooperation. We addressed this research gap by leveraging functional near-infrared spectroscopy (fNIRS) to record the brain activity of triad members in a group simultaneously. Triads were instructed to analyze an ancient Chinese poem either cooperatively or independently. Four main findings emerged. First, we observed significant within-group neural synchronization (GNS) in the left superior temporal cortex, supramarginal gyrus, and postcentral gyrus during cooperative learning compared to independent learning. Second, the enhancement of GNS in triads was amplified when a consensus was reached (vs. elaboration or argument) during cooperative learning. Third, GNS was predictive of learning outcome at an early stage (156-170 s after learning was initiated). Fourth, social factors such as social closeness (e.g., how much learners liked one other) were reflected in GNS and co-varied with learning engagement. These results provide neurophysiological support for Piagets theory of cognitive development and favor the notion that successful learning through cooperation involves dynamic consensus building, which is captured in neural patterns shared across learners in a group. Significance StatementConverging evidence has shown that cooperative learning is more effective than independent learning. An influential pedagogical theory postulates that learners benefit from cooperation through different forms of cognitive elaboration, such as providing elaborated clarifications to others. Alternatively, Piagets theory of cognitive development posits that cooperation encourages learners with diverse opinions to reach a consensus during the learning process. Here, we report that unlike individuals who worked alone, the brains of students who worked cooperatively with one another became synchronized. This within-group neural synchronization (GNS) was magnified when learners built mutual consensuses. These findings suggest that successful cooperative learning involves dynamic consensus building, which is reflected in the interpersonal coordination of cerebral activity.

neuroscience↗

bioRxiv2021

T1SEstacker: A tri-layer stacking model effectively predicts bacterial type 1 secreted proteins based on C-terminal non-RTX-motif sequence features

The proteins secreted through type 1 secretion systems often play important roles in pathogenicity of various gram-negative bacteria. However, the type 1 secretion mechanism remains unknown. In this research, we observed the sequence features of RTX proteins, a major class of type 1 secreted substrates. We found striking non-RTX-motif amino acid composition patterns at the C-termini, most typically exemplified by the enriched [FLI][VAI] at the most C-terminal two positions. Machine-learning models, including deep-learning models, were trained using these sequence-based non-RTX-motif features, and further combined into a tri-layer stacking model, T1SEstacker, which predicted the RTX proteins accurately, with a 5-fold cross-validated sensitivity of ~0.89 at the specificity of ~0.94. Besides substrates with RTX motifs, T1SEstacker can also well distinguish non-RTX-motif type 1 secreted proteins, further suggesting their potential existence of common secretion signals. In summary, we made comprehensive sequence analysis on the type 1 secreted RTX proteins, identified common sequence-based features at the C-termini, and developed a stacking model that can predict type 1 secreted proteins accurately.

microbiology↗

bioRxiv2021

Three-dimensional in vitro model of the device-tissue interface reveals innate neuroinflammation can be mitigated by antioxidant ceria nanoparticles

The recording instability of neural implants due to neuroinflammation at the device-tissue interface (DTI) is a primary roadblock to broad adoption of brain-machine interfaces. While a multiphasic immune response, marked by glial scaring, oxidative stress (OS), and neurodegeneration, is well-characterized, the independent contributions of systemic and local "innate" immune responses are not well-understood. Three-dimensional primary neural cultures provide a unique environment for studying the drivers of neuroinflammation by decoupling the innate and systemic immune systems, while conserving an endogenous extracellular matrix and structural and functional network complexity. We created a three-dimensional in vitro model of the DTI by seeding primary cortical cells around microwires. Live imaging of microtissues over time revealed independent innate neuroinflammation, marked by increased OS, decreased neuronal density, and increased functional connectivity. We demonstrated the use of this model for therapeutic screening by directly applying drugs to neural tissue, bypassing low bioavailability through the in vivo blood brain barrier. As there is growing interest in long-acting antioxidant therapies, we tested efficacy of "perpetual" antioxidant ceria nanoparticles, which reduced OS, increased neuronal density, and protected functional connectivity. Overall, our avascular in vitro model of the DTI exhibited symptoms of OS-mediated innate neuroinflammation which were mitigated by antioxidant intervention.

bioengineering↗

bioRxiv2021

Cold protection allows local cryotherapy in a clinical-relevant model of traumatic optic neuropathy

Therapeutic hypothermia (TH) is potentially an important therapy for central nervous system (CNS) trauma. However, its clinical application remains controversial, hampered by two major factors: 1) Many of the CNS injury sites, such as the optic nerve (ON), are deeply buried, preventing access for local TH. The alternative is to apply TH systemically, which significantly limits the applicable temperature range. 2) Even with possible access for "local refrigeration", cold-induced cellular damage offsets the benefit of TH. Here we present a clinically translatable model of traumatic optic neuropathy (TON) by applying clinical trans-nasal endoscopic surgery to goats and non-human primates. This model faithfully recapitulates clinical features of TON such as the injury site (pre-chiasmatic ON), the spatiotemporal pattern of neural degeneration, and the accessibility of local treatments with large operating space. We also developed a computer program to simplify the endoscopic procedure and expand this model to other large animal species. Moreover, applying a cold-protective treatment, inspired by our previous hibernation research, enables us to deliver deep hypothermia (4{degrees}C) locally to mitigate inflammation and metabolic stress (indicated by the transcriptomic changes after injury) without cold-induced cellular damage, and confers prominent neuroprotection both structurally and functionally. Intriguingly, neither treatment alone was effective, demonstrating that in situ deep hypothermia combined with hibernation-mimicking cold protection constitutes a breakthrough for TH as a therapy for TON and other CNS traumas.

neuroscience↗

bioRxiv2021

A trimeric NTD and RBD SARS-CoV-2 subunit vaccine induced protective immunity in CAG-hACE2 transgenic mice and rhesus macaques

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to significant public health, economic and social problems. Development of effective vaccines is still a priority to contain the virus and end the global pandemic. In this study, we reported that ReCOV, a recombinant trimeric NTD and RBD two-component SARS-CoV-2 subunit vaccine adjuvanted with BFA03 (an AS03-like squalene adjuvant), induced high levels of neutralizing antibodies against SARS-CoV-2 and the circulating variants in mice, rabbits and rhesus macaques. Notably, two-dose immunizations of ReCOV provided complete protection against challenge with SARS-CoV-2 in hACE2 transgenic mice and rhesus macaques, without observable antibody-dependent enhancement of infection. These results support further clinical development of ReCOV and the vaccine is currently being evaluated in a phase I clinical trial in New Zealand (NCT04818801).

immunology↗

bioRxiv2021

Brilacidin, a COVID-19 Drug Candidate, demonstrates broad-spectrum antiviral activity against human coronaviruses OC43, 229E and NL63 through targeting both the virus and the host cell

Brilacidin, a mimetic of host defense peptides (HDPs), is currently in phase 2 clinical trial as an antibiotic drug candidate. A recent study reported that brilacidin has antiviral activity against SARS-CoV-2 by inactivating the virus. In this work, we discovered an additional mechanism of action of brilacidin by targeting heparan sulfate proteoglycans (HSPGs) on host cell surface. Brilacidin, but not acetyl brilacidin, inhibits the entry of SARS-CoV-2 pseudovirus into multiple cell lines, and heparin, a HSPG mimetic, abolishes the inhibitory activity of brilacidin on SARS-CoV-2 pseudovirus cell entry. In addition, we found that brilacidin has broad-spectrum antiviral activity against multiple human coronaviruses (HCoVs) including HCoV-229E, HCoV-OC43, and HCoV-NL63. Mechanistic studies revealed that brilacidin has a dual antiviral mechanism of action including virucidal activity and binding to coronavirus attachment factor HSPGs on host cell surface. Brilacidin partially loses its antiviral activity when heparin was included in the cell cultures, supporting the host-targeting mechanism. Drug combination therapy showed that brilacidin has a strong synergistic effect with remdesivir against HCoV-OC43 in cell culture. Taken together, this study provides appealing findings for the translational potential of brilacidin as a broad-spectrum antiviral for coronaviruses including SARS-CoV-2.

pharmacology and toxicology↗

bioRxiv2021

mTOR-neuropeptide Y signaling sensitizes nociceptors to drive neuropathic pain

Neuropathic pain is a refractory condition that involves de novo protein synthesis in the nociceptive pathway. The mechanistic target of rapamycin (mTOR) is a master regulator of protein translation; however, mechanisms underlying its role in neuropathic pain remain elusive. Using spared nerve injury-induced neuropathic pain model, we found that mTOR is preferentially activated in large-diameter dorsal root ganglion (DRG) neurons and spinal microglia. However, selective ablation of mTOR in DRG neurons, rather than microglia, alleviated neuropathic pain. We show that injury- induced mTOR activation promoted transcriptional induction of NPY likely via signal transducer and activator of transcription 3 (STAT3) phosphorylation. NPY further acted primarily on Y2 receptors (Y2R) to enhance nociceptor excitability. Peripheral replenishment of NPY reversed pain alleviation upon mTOR removal, whereas Y2R antagonists prevented pain restoration. Our findings reveal an unexpected link between mTOR and NPY in promoting nociceptor sensitization and neuropathic pain, through NPY/Y2R signaling-mediated intra-ganglionic transmission.

neuroscience↗

bioRxiv2021

High-resolution spatiotemporal transcriptomic maps of developing Drosophila embryos and larvae

Drosophila has long been a successful model organism in multiple fields such as genetics and developmental biology. Drosophila genome is relatively smaller and less redundant, yet largely conserved with mammals, making it a productive model in studies of embryogenesis, cell signaling, disease mechanisms, etc. Spatial gene expression pattern is critical for understanding of complex signaling pathways and cell-cell interactions, whereas temporal gene expression changes need to be tracked during highly dynamic activities such as tissue development and disease progression. Systematic studies in Drosophila as a whole are still impeded by lack of these spatiotemporal transcriptomic information. Drosophila embryos and tissues are of relatively small size, limiting the application of current technologies to comprehensively resolve their spatiotemporal gene expression patterns. Here, utilizing SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq), we dissected the spatiotemporal transcriptomic changes of developing Drosophila with high resolution and sensitivity. Our data recapitulated the spatial transcriptomes of embryonic and larval development in Drosophila. With these data, we identified known and previously undetected subregions in several tissues during development, and revealed known and potential gene regulatory networks of transcription factors within their topographic background. We further demonstrated that Stereo-seq data can be used for 3D reconstruction of Drosophila embryo spatial transcriptomes. Our data provides Drosophila research community with useful resources of spatiotemporally resolved transcriptomic information across developmental stages.

developmental biology↗

bioRxiv2021

High Resolution Nanostructure with Two-stages of Exponential Energy Dissipation at the Ultrathin Osteochondral Interface Tissue of Human Knee Joint

Cartilage adheres to subchondral bone via a specific osteochondral interface tissue where forces are transferred from soft cartilage to hard bone without fatigue damage over a lifetime of load cycles. However, the fine structure and mechanical properties of osteochondral interface tissue remain unclear. Here, we identified an ultrathin [~]20-30 m calcified region with two-layered micro-nano structures of osteochondral interface tissue in human knee joint, which exhibited characteristic biomolecular compositions and complex nanocrystals assembly. Within this region, an exponential increase of modulus (3 orders of magnitude) was conducive to the force transmission which was verified by finite element simulations. The nanoscale heterogeneity of hydroxyapatite, along with enrichment of elastic-responsive protein-titin which is usually present in muscle, endowed the osteochondral tissue with excellent energy dissipation and fatigue resistance properties. Our results provide potential design for high-performance interface materials for osteochondral interface regeneration and functional coatings.

bioengineering↗

bioRxiv2021

Serine/arginine-rich splicing factor 7 plays oncogenic roles through specific regulation of m6A RNA modification

Serine/Arginine-Rich Splicing Factor 7 (SRSF7), which is previously recognized as a splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N6-methyladenosine (m6A) co-methylation network analysis across diverse cell lines, we found SRSF7 positively correlated with glioblastoma cell-specific m6A methylation. We then proved SRSF7 is a novel m6A regulator that specifically facilitates the m6A methylation near its binding sites on the mRNAs involved in cell proliferation and migration through recruiting methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of glioblastoma cells largely dependent on the m6A methyltransferase. The two single-nucleotide m6A sites on PBK are regulated by SRSF7 and partially mediate the effects of SRSF7 on glioblastoma cells through recognition by IGF2BP2. Together, our discovery revealed a novel role of SRSF7 in regulating m6A and timely confirmed the existence and functional importance of RNA binding protein (RBP) mediated specific regulation of m6A.

molecular biology↗