If material is not included in the articles Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Article Wu, C. et al. Epitranscriptomic profiling of N6-methyladenosine-related RNA methylation in infant rhesus macaques after multiple sevoflurane anesthesia. Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19. The Microbiology and Immunology programme involves immune cells, bacteria, fungi, viruses and parasites. F Human m6A-mRNA and lncRNA epitranscriptomic microarray reveal function of RNA methylation in hemoglobin H-constant spring disease. (p-value=0.013, Fig. Our findings that inhibition of mTOR in replicative senescent hGFs partially decreased the SA--Gal staining (Figure 3(a)) and reduced the cytokine (IL-6 and IL-8; Figures 3(b) and 3(d)) expression appear consistent with other reports that rapamycin reduces SASP in different kinds of cellular senescence [27, 28]. We first investigated in our discovery cohorts whether SARS-CoV-2 infection is associated with alpha diversity of the human microbiome at the nrMAG-level. Importantly, we found that some of these species were previously reported (including in the original study Yeoh et al.) 1, pp. Coverslips were mounted with Fluoroshield with DAPI (Sigma-Aldrich) and -smooth muscle actin (Sigma-Aldrich) to allow visualization of the cell nuclei and cellular morphology. Stincone, A. et al. 430439, 2015. Some sequencers have their own proprietary quality encoding but most have adopted Phred-33 encoding. 1)29,30. Statistical source data for Supplementary Fig. Seemann, T. Prokka: rapid prokaryotic genome annotation. Genetically encoded chemical probes in cells reveal the binding path of urocortin-I to CRF class B GPCR. S14a). To better understand those results, we also outputted the top-30 most important features ranked based on the mean decrease accuracy (MDA). Replicative senescent hGFs had a higher level of intracellular ROS compared with the control (Figure 4(a), left panel). Purification and quantification of HfqRNA binding. Dynamic landscape and evolution of m6A methylation in human. Ke, S. et al. Alterations in the human oral and gut microbiomes and lipidomics in COVID-19. RNA methylomes reveal the m6A-mediated regulation of DNA demethylase gene SlDML2 in tomato fruit ripening. Cell 157, 121141 (2014). The universal nature of our microbiome-derived signature suggests that some key microbial species might play very important roles in the pathophysiology of SARS-CoV-2 infection. Clin. All the sequencing data were downloaded from online repositories or links provided in the original publications, but some metadata were acquired after personal communication with the authors. (a sample size n=65) and Yeoh et al. So we also examined the anti-inflammatory ability of hGFs against P. gingivalis when pretreated with rapamycin. Mouse Maternal High-Fat Intake Dynamically Programmed mRNA mA Modifications in Adipose and Skeletal Muscle Tissues in Offspring. Analysis of these results indicates that rapamycin partially reversed the senescent progress in hGFs. Olarerin-George, A. O. 28a | 37079 Goettingen | Germany. 1. b) Denaturing urea-PAGE demonstrating the pre-crRNA cleavage by dPsCas13b-WT and dPsCas13b-Ala-mutants speculatively involved in the pre-crRNA processing. Protoc. Suppression of m6A reader Ythdf2 promotes hematopoietic stem cell expansion. In this study we genetically encoded latent bioreactive unnatural amino acids into proteins to react with bound RNA by proximity-enabled reactivity and demonstrated genetically encoded chemical crosslinking of proteins with target RNA (GECX-RNA) in vivo. Moreover, an earlier study (86 COVID-19 patients and 57 healthy controls, United Arab Emirates) reported that the pentose phosphate pathway was significantly upregulated on COVID-19 patient microbiome samples using 16S rRNA gene sequencing together with a phylogenetic investigation of communities by reconstructing unobserved state (PICRUSt)72. CAS S13d). To further characterize the relation between the human gut microbiome and COVID-19, we applied the generalized microbe-phenotype triangulation (GMPT) method to move beyond the standard association analysis46 (Fig. m6A modifications regulate intestinal immunity and rotavirus infection. A. Bernadotte, V. M. Mikhelson, and I. M. Spivak, Markers of cellular senescence. Microorganisms https://doi.org/10.3390/microorganisms9061292 (2021). S13a). Uncropped images, unprocessed gels, unprocessed western blots and statistical source data. Get the most important science stories of the day, free in your inbox. Excessive miR-25-3p maturation via N6-methyladenosine stimulated by cigarette smoke promotes pancreatic cancer progression. 149, no. Coherently, the human gut microbiome of patients with COVID-19 in our study exhibited overall decreased alpha diversity at the nrMAGs level compared to the Non-COVID-19 healthy controls. Med. Statistical source data for Supplementary Fig. Functional profiling of COVID-19 respiratory tract microbiomes, Multi-kingdom gut microbiota analyses define COVID-19 severity and post-acute COVID-19 syndrome, Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions, Dysbiosis and structural disruption of the respiratory microbiota in COVID-19 patients with severe and fatal outcomes, Microbiome-Transcriptome Interactions Related to Severity of Respiratory Syncytial Virus Infection, Temporal association between human upper respiratory and gut bacterial microbiomes during the course of COVID-19 in adults, Integrated characterization of SARS-CoV-2 genome, microbiome, antibiotic resistance and host response from single throat swabs, Clinical practices underlie COVID-19 patient respiratory microbiome composition and its interactions with the host, The human respiratory tract microbial community structures in healthy and cystic fibrosis infants, https://ngdc.cncb.ac.cn/gsa/browse/CRA003271, https://figshare.com/s/a426a12b463758ed6a54, http://huttenhower.sph.harvard.edu/humann_data/, https://doi.org/10.1053/j.gastro.2021.10.013, https://doi.org/10.1101/2022.01.06.475215, https://doi.org/10.3390/microorganisms9061292, https://doi.org/10.1172/jci.insight.140327, https://doi.org/10.1093/bioinformatics/btz848, Description of Additional Supplementary Files, http://creativecommons.org/licenses/by/4.0/. Clinical characteristics of imported cases of coronavirus disease 2019 (COVID-19) in Jiangsu province: a multicenter descriptive study. The aim of present study is to evaluate the effects of mTOR inhibition on preserving the proliferative potential, enhancing anti-inflammatory reaction and alleviating oxidative stresses on human gingival fibroblasts (hGFs). The m6A pathway protects the transcriptome integrity by restricting RNA chimera formation in plants. m6A Methylation Analysis of Differentially Expressed Genes in Skin Tissues of Coarse and Fine Type Liaoning Cashmere Goats. Sunagawa, S. et al. 35, 9911011 (2016). CAS Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. The two are characterized by differential sensitivity to rapamycin. Nat. ), respectively. We would like to thank Dr. Yun Kit Yeoh and Dr. Siew C Ng for sharing the phenotypic data with us. LncNAP1L6 activates MMP pathway by stabilizing the m6A-modified NAP1L2 to promote malignant progression in prostate cancer. Source data for Sanger sequencing in Supplementary Fig. Microbiol. 436446, 2009. N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells. Moreover, we identified a set of nrMAGs with a putative causal role in the clinical manifestations of COVID-19 and revealed their functional pathways that potentially interact with SARS-CoV-2 infection. 919, 2007. Environ Microbiol. Chem. 50, 27672776 (2017). Metabolites https://doi.org/10.3390/metabo11050327 (2021). About TRADES: Targeted RNA Demethylation by SunTag System. Here positive (negative) Spearman correlation coefficient () represent the permissive (protective) nrMAGs of COVID-19 severity. S18). CAS Biosci. It is said that mTORC1 controls protein synthesis and responses to multifarious cellular stresses, while mTORC2 regulates cell survival. (c) Apoptosis of hGFs is examined by an FITC Annexin V Apoptosis Detection Kit (n.s.. Primer sequence used for polymerase chain reaction amplifications. designed and conducted the experiments, analysed the data and wrote the manuscript; N.W. The significant differences in the days before replicative senescence, the maximum cumulative population doublings, and the percentage of apoptotic cells between the control group and rapamycin-treated group were analyzed using unpaired two-tailed Students t-test. Resources for editing files on the HPC. Protein Sci. Padilla-Sanchez, V. SARS-CoV-2 structural analysis of receptor binding domain new variants from united kingdom and South Africa. Alevin is a tool integrated with the salmon software that introduces a family of algorithms for quantification and analysis of 3 tagged-end single-cell sequencing data. RNA Biol. One key advantage of this strategy is that it allows recovery of genomes for microorganisms that have yet to be isolated and cultured and hence are absent from the current reference genome databases. & Woodson, S. A. B MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m6A-YTHDF1-dependent mechanism. m6A RNA modification modulates gene expression and cancer-related pathways in clear cell renal cell carcinoma. Front. ALKBH5-mediated m6A modification of lncRNA KCNQ1OT1 triggers the development of LSCC via upregulation of HOXA9. (Fig. Profiling of RNA N6-methyladenosine methylation during follicle selection in chicken ovary. 1929, 2016. In fact, an estimated 4050% of human gut species lack a reference genome24,25. C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. PeerJ 3, e1165 (2015). Taken together, lifespan regulation via the mTOR signaling pathway is conserved, growth hormone and IGF-1 should be clinically applied with caution. This strategy has been adopted in several studies to provide genomic insights into microbial populations that are critical to human health and disease27,28. RNA m6A Modification Changes in Postmortem Nucleus Accumbens of Subjects with Alcohol Use Disorder: A Pilot Study. MYC Regulation of D2HGDH and L2HGDH Influences the Epigenome and Epitranscriptome. 3 Examples of GRIP-seq data for m. 6, 191 (2021). Parks, D. H. et al. First, MAGs were divided into primary clusters using Mash86 at a 90% Mash ANI. Our major goals were to construct a COVID-19 related metagenomic genome catalog to identify novel taxa and strain-level differences that are likely related to the clinical manifestations of SARS-COV-2 infection. Moreover, we found that the pentose phosphate pathway also showed higher abundance in COVID-19 patients from Zhang et al. Alteration of N6-methyladenosine epitranscriptome profile in unilateral ureteral obstructive nephropathy. RNA m6A modification orchestrates a LINE-1-host interaction that facilitates retrotransposition and contributes to long gene vulnerability. Nat. Baker, J. L. et al. 6, 26 (2011). Interestingly, those protective nrMAGs also showed a similar abundance distribution between patients with COVID-19 and Non-COVID-19 controls in the study of Zuo et al.18 (Fig. The m6A methylation regulates gonadal sex differentiation in chicken embryo. 38, 226236 (2015). https://github.com/Shall-We-Dance/GRIP-seq, https://doi.org/10.1038/s41557-022-01059-z. In addition, when infected by prominent periodontal pathogens, Porphyromonas gingivalis (ATCC 33277), rapamycin-pretreated groups decreased the expression of inflammatory cytokines (IL-6 and IL-8) compared with the control group. Genetically encoding photocaged quinone methide to multitarget protein residues covalently in vivo. Regulation of AR mRNA translation in response to acute AR pathway inhibition. Expanded catalog of microbial genes and metagenome-assembled genomes from the pig gut microbiome. Treatment of cancer cells with Lapatinib negatively regulates general translation and induces stress granules formation. CAS Our analysis did not exclude these nasopharyngeal microbiome samples as they did contribute unique high-quality MAGs to our nrMAGs collection. Positive charged residues in PsCas13b located on -sheets 5 and 6 (367K, 370K, 378R, 380R) are marked with purple squares. 9696, pp. Camb. These authors contributed equally: Wei Sun, Nanxi Wang. It is important to note that these protective bacteria have also been reported to be related to SARS-CoV-2 infection. The differentially abundant nrMAGs pool were originated from these pairwise analyses. Deciphering the "m6A Code" via Antibody-Independent Quantitative Profiling. https://doi.org/10.3390/jcm9061753 (2020). Using replicative senescent human gingival fibroblasts, we demonstrated that the mTOR inhibition partially reversed the aging process and elevated the anti-inflammatory ability of gingival fibroblasts. KofamKOALA: KEGG Ortholog assignment based on profile HMM and adaptive score threshold. Front Microbiol. N6-Methyladenosine on mRNA facilitates a phase-separated nuclear body that suppresses myeloid leukemic differentiation. A link between FTO, ghrelin, and impaired brain food-cue responsivity. Previous studies demonstrated that SARS-CoV-2 infection is associated with the alpha diversity of the human gut12,32,33 and oral34,35 microbiome at the genus- or species-level. An alternative strategy to analyze WMS sequencing data is to reconstruct metagenome-assembled genomes (MAGs) through de novo assembly and binning26. Olm, M. R., Brown, C. T., Brooks, B. In addition, SARS-CoV-2 infection was found to be associated with changes in the regulation of the pentose phosphate pathway in both in vivo (Caco-2 cells)66 and in vitro (ferret model)67 studies. Q Correspondence to Cell 69, 354369 (2018). Cells go to senesce and gradually lose proliferative capacity while cell cycle is irreversibly arrested but metabolic activity is not. The main findings from the discovery cohorts were then validated using the data from three independent cohorts. Multiplexed profiling facilitates robust m6A quantification at site, gene and sample resolution. Struct. STAR: ultrafast universal RNA-seq aligner. Then, each primary cluster was used to form secondary clusters at the threshold of 99% ANI with at least 30% overlap between genomes. O 12, 712081 (2021). Gerstberger, S., Hafner, M. & Tuschl, T. A census of human RNA-binding proteins. X Notably, this study sheds important light on the ability of nrMAGs to predict the date of negative RT-qPCR result of patients with COVID-19. The secondary structure of BzoCas13b is shown above the sequence28. We detected intracellular DCF level using a flow cytometer. When salmon die, those nutrients are gobbled up by insects, plants, mammals, and birds. Genetically encoded chemical crosslinking of RNA in vivo. 290, 2490224913 (2015). Bioactive peptide inhibits acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m6A demethylation of EIF4EBP1 and MLST8 mRNA. HPCRunner; BioX Workflow; ChipSeq analysis. All GRIP-seq data are available in the Sequence Read Archive through accession number PRJNA797913. Gut microbiota interplay with COVID-19 reveals links to host lipid metabolism among middle eastern populations. Importantly, this analysis was performed with 5-fold cross-validation and the data were randomly split into training and test sets 50 times. Dissertations & Theses from 2022. There are still few studies showing the effects of mTOR inhibition on a primate model. nf-core/rnaseq is a bioinformatics pipeline that can be used to analyse RNA sequencing data obtained from organisms with a reference genome and annotation.. On release, automated continuous integration tests run the pipeline on a full-sized dataset obtained from the ENCODE Project Consortium on the AWS cloud infrastructure. Biomed. Principal component analysis revealed quite different metabolic potentials between permissive and protective nrMAGs (Fig. Reverse-transcription-termination sites (RT-termination sites) from GRIP-seq were marked as yellow triangles. Appl. Common uses are to filter bases or entire reads if a particular quality threshold isnt met. Thank you for visiting nature.com. Syst. S22a) and Yeoh et al. Smargon, A. Article D [jump to top]. Given the fact that many patients recovering from SARS-CoV-2 infection have experienced prolonged COVID-19 symptoms56, we hypothesize that long-lasting disease symptoms may be associated with changes in the gut microbiome but this needs to be explored further. Transcript and gene-level abundance estimates got by running salmon(v0.15.0). 303314, 2016. Article This may be due to the small sample size and the fact that Non-COVID-19 controls are not health controls in one of the nasopharyngeal microbiome datasets (Liu et al.36). S15c, d). Notably, we found the classifications trained with samples from Yeoh et al. Dobin, A. et al. As shown in results, inhibition of mTOR activity with the selective inhibitor, rapamycin, preserved the proliferative capacity, delayed the onset of senescence, and remitted the inflammatory response through alleviating oxidative stress. Enriched opportunistic pathogens revealed by metagenomic sequencing hint potential linkages between pharyngeal microbiota and COVID-19. 1, pp. a To understand the relation between human microbiome and COVID-19 via metagenome-assembled genomes (MAGs), we collected a total of 514 (6 cohorts) and 341 (3 cohorts) shotgun metagenomic sequencing data on the discovery and validation cohorts, respectively. Shannon diversity (a) and within group BrayCurtis dissimilarity (b) of the human microbiome at the nrMAG-level from each study. i The fraction of common nrMAGs on patients with COVID-19 over timefrom the study of Yeoh et al. Commun. Trillions of microbes live inside the GI tract. The volatile and heterogeneous gut microbiota shifts of COVID-19 patients over the course of a probiotics-assisted therapy. Trends Genet. Transcriptome-wide m6A methylome during osteogenic differentiation of human adipose-derived stem cells. The m6A(m)-independent role of FTO in regulating WNT signaling pathways. ISSN 2041-1723 (online). Li, S. et al. Consistent with a previous study36, we found no significant differences between COVID-19 patients and Non-COVID-19 controls in the nasopharyngeal microbiome samples (Fig. Importantly, our study mainly focused on two discovery cohorts (Zuo et al.18 and Yeoh et al.19) and three validation cohorts (Zhang et al.41, Xu et al.39, and Li et al.22) with well-defined case and control subjects. However, little is known about the relation between the human microbiome and COVID-19, largely due to the fact that most previous studies fail to provide high taxonomic resolution to identify microbes that likely interact with SARS-CoV-2 infection. 6b), including Enterocloster bolteae (3 nrMAGs), Anaeroglobus micronuciformis, Hungatella effluvii (3 nrMAGs), and Enterococcus_B faecium. Nat. SGBs containing at least one reference genome (or metagenome-assembled genome) in the Genome Taxonomy Database (GTDB) were considered as known SGBs. METTL3 regulates m6A methylation of PTCH1 and GLI2 in Sonic hedgehog signaling to promote tumor progression in SHH-medulloblastoma. J. Jumper, J. et al. METTL3-dependent N6-methyladenosine RNA modification mediates the atherogenic inflammatory cascades in vascular endothelium. (a) Western blot analysis of hGFs treated with rapamycin for 72h and 30d. mTOR inhibition is shown by the levels of pS6. M. A. Reynolds, Modifiable risk factors in periodontitis: at the intersection of aging and disease, Periodontology 2000, vol. Merge abundence data of each sample to bulid counts matrices,which is the input file of EdgeR for downstream analysis. We introduce Salmon, a lightweight method for quantifying transcript abundance from RNAseq reads. YTHDF2 promotes spermagonial adhesion through modulating MMPs decay via m6A/mRNA pathway. PLoS One 16, e0247041 (2021). Moreover, we found multiple microbial genomes have the potential to use this pathway (Figs. Notably, we found for the first time that COVID-19 patients lost many strains (nrMAGs) for certain microbial species when compared to Non-COVID-19 controls in both the discovery and validation cohorts. https://doi.org/10.1038/s41467-022-32991-w, DOI: https://doi.org/10.1038/s41467-022-32991-w. Hwang, H.-W. et al. Dierks D, Garcia-Campos MA, Uzonyi A, Safra M, Edelheit S, Rossi A, Sideri T, Varier RA, Brandis A, Stelzer Y, van Werven F, et al. ; If you imported quantification data with tximeta, which produces a SummarizedExperiment with Google Scholar. Asterisks indicate the statistical significant levels of NS (, , , and ). For example, Citrobacter freundii was found to be significantly enriched in COVID-19 patients with fever57. Mettl14-mediated m6A Modification Facilitates Liver Regeneration by Maintaining Endoplasmic Reticulum Homeostasis. J Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. METTL3 Promotes the Progression of Gastric Cancer via Targeting the MYC Pathway. That is: whats the average score of all bases for an individual read? MicroRNA-501-3p inhibits the proliferation of kidney cancer cells by targeting WTAP. m6A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells. Laozi see Laozi; Neo-Daoism see Neo-Daoism; religious (Fabrizio Pregadio) ; Zhuang Zi see Zhuangzi; Darwin, Charles from Origin of Species to Descent of Man see evolution: from Currently, the role of angiotensin-converting enzyme 2 (ACE2) in the invasion of host cells by SARS-CoV-2 via its spike protein is well-established7, and ACE2 is also highly expressed in the small intestine and colon4,8. Genome Res. The elderly also seem to have increased susceptibility to periodontitis [36]. 4, 240 (2021). Senescent cells are hypothesized to involve disruption of tissue homeostasis because of a multifarious senescence-associated secretory phenotype (SASP). Peer reviewer reports are available. (b) The results of real-time PCR show the mRNA expression of antioxidant components Cat, Sod2, and Prdx3 (, Rapamycin enhances the anti-inflammatory ability of human gingival fibroblasts. Applying GECX-RNA to the RNA chaperone Hfq in Escherichia coli identified target RNAs with amino acid specificity. Borkh). Nevertheless, given the large uncultured diversity still remaining in the human gut microbiome and deficiency of both annotated genes and reference genomes, having a high-quality genome catalog substantially enhances the resolution and accuracy of metagenome-based COVID-19 studies. Structural basis for the discriminative recognition of N6-methyladenosine RNA by the human YT521-B homology domain family of proteins. Google Scholar. Advances in CLIP technologies for studies of proteinRNA Interactions. PubMed Yang-Yu Liu. The codes for construction of the MAGs catalog and statistical analyses and visualization are available in the GitHub repository (https://github.com/Owenke247/COVID-19) or the Zenodo database (https://doi.org/10.5281/zenodo.6824864). Importantly, we observed some opportunistic pathogens were associated with the progression of COVID-19, including nrMAGs from Klebsiella quasivariicola43, Klebsiella pneumoniae44, and Escherichia coli45. Annu. Nat. 31, 312322 (2021). The results of real time-PCR (Figure 4(b)) show that the mRNA expression of the antioxidant components catalase (Cat), manganese superoxide dismutase (Sod2), and peroxiredoxin-3 (Prdx3) decrease while in continuously replicative culture (high passage versus low passage). synthesized FSY and SFY, performed the SFY reactions with NMPs in vitro and analysed the data; L.J. 6b and Supplementary Data2. To date, several studies, based on 16S rRNA gene sequencing, have demonstrated that the human upper respiratory and gut microbiome are broadly altered in patients with COVID-1911,12,13,14,15,16. Xu, R. et al. Almost every QC software package use these. Leukemogenic Chromatin Alterations Promote AML Leukemia Stem Cells via a KDM4C-ALKBH5-AXL Signaling Axis. N6-methyladenosine modification of HCV RNA genome regulates cap-independent IRES-mediated translation via YTHDC2 recognition. Mettl3-mediated mRNA m6A methylation promotes dendritic cell activation. S Holmqvist, E. et al. 24, 104880 (2021). 19, 327341 (2018). Atom; SSH Mounts; Neovim; SLURM; Modules; Gencore Infrastructure. B. Berletch, L. G. Andrews, and T. O. Tollefsbol, Aging cell culture: methods and observations, Methods in Molecular Biology, vol. All authors approved the manuscript. Belkaid, Y. S9e, f). 25, no. m6A demethylase ALKBH5 controls CD4+ T cell pathogenicity and promotes autoimmunity. Cell proliferation analysis was measured using Cell Counting Kit-8 (CCK-8) (WST-8; Dojindo, Kumamoto, Japan) and absorbance at 450nm was detected for each well by a microplate reader (BioTek Instruments, Winooski, VT, USA). Fresh tissue specimens (from 5 individuals aged 1825 years old) were obtained during crown-lengthening surgery from the Department of Periodontology at the Ninth Peoples Hospital, Shanghai Jiao Tong University School of Medicine, between April and September 2015. Briefly, we trained our machine learning model with samples from the cohort of Zuo et al. 392U108, 2009. The m6A reader YTHDC2 inhibits lung adenocarcinoma tumorigenesis by suppressing SLC7A11-dependent antioxidant function. Aromatic amino acids in the juxtamembrane domain of severe acute respiratory syndrome coronavirus spike glycoprotein are important for receptor-dependent virus entry and cell-cell fusion. Microbiol 45, 27612764 (2007). METTL3 promotes colorectal carcinoma progression by regulating the m6A-CRB3-Hippo axis. Gastroenterology 158, 18311833.e1833 (2020). Previous efforts have linked human microbiome diversity and COVID-1911,14,34. RNA m6 A methylation regulates virus-host interaction and EBNA2 expression during Epstein-Barr virus infection. The tree was visualized using iTOL (https://itol.embl.de/)89. J. Biochem. Chen, C. et al. Discovery of Small Molecules that Activate RNA Methylation through Cooperative Binding to the METTL3-14-WTAP Complex Active Site. Among these samples in the discovery cohorts, we have 404 (78.60%) and 110 (21.40%) samples from COVID-19 patients and Non-COVID-19 controls (Fig. Melatonin restores the pluripotency of long-term-cultured embryonic stem cells through melatonin receptor-dependent m6A RNA regulation. 3a and Fig. This study was supported by the National Natural Science Foundation of China (Grant no. Article 3g). The current study has several limitations. Notably, our study identified a set of COVID-19 related nrMAGs and their determinants (i.e., permissive and protective) potentially involved in disease pathogenesis. Sci. S12c). To explore whether the strain-level diversity within the same species is related to COVID-19, we analyzed data from the two discovery cohorts (Zuo et al.18 and Yeoh et al.19) as well as the three validation cohorts (Zhang et al.41, Xu et al.39, and Li et al.22). 2, pp. (or Zuo et al. Proc. 4, pp. Moreover, three specific nrMAGs were identified (from Mediterraneibacter_A butyricigenes and Eisenbergiella sp900066775) as common features between the two datasets. Short-term mTOR inhibition: high-passage hGFs were treated with 20nmol/L rapamycin (Sigma-Aldrich Inc., St. Louis, MO, USA) once and harvested after 72 hours for further experiments. 7432, pp. Figuratively speaking, our results suggested that mTOR inhibition preserved the Ki-67 staining (a well-known marker of proliferation; Figure 1(d)) but the well-defined flat cell morphology did not change (Figure 2(d), shown by actin staining) in replicative senescent hGFs. Nature Chemistry thanks Ryan Flynn, Stephen Fried and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. and Y.S. Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Li, Q. et al. There are now several methods available for estimating transcript abundance in a genome-free manner, and these include alignment-based methods (aligning reads to the transcript assembly) and alignment-free methods (typically examining k-mer abundances in the reads and in the resulting assemblies). We identified multiple species with highly similar genomes from those permissive nrMAGs (Fig. Parks, D. H. et al. We found that the classification models trained with the data of Yeoh et al.19 achieved an overall reasonable classification performance on those validation cohorts (Fig. Liu, L. et al. 71, 706712 (2020). Cell Biol. Uhln, M. et al. Although 16S rRNA gene sequencing provides valuable insights into the general characteristics of the human microbiota, it does not offer the taxonomic resolution needed to capture sufficient sequence variation to discriminate between closely related taxa17. Biol. To obtain the view of the microbial community at the species level, we first organized 11,584 MAGs into species-level genome bins (SGBs) at an ANI (average nucleotide identity) threshold of 95%, resulting in a total of 872 SGBs, of which 160 (18.35%) SGBs represented species without any available genomes from the Genome Taxonomy Database (GTDB)31 and were defined as unknown SGBs (uSGB, Fig. bioRxiv https://doi.org/10.1101/2022.01.06.475215 (2022). These nrMAGs were taxonomically annotated using GTDB-Tk based on the Genome Taxonomy Database. R-2-hydroxyglutarate attenuates aerobic glycolysis in leukemia by targeting the FTO/m6A/PFKP/LDHB axis. 17, no. 17, 909915 (2010). Google Scholar. FIONA1 is an RNA N6-methyladenosine methyltransferase affecting Arabidopsis photomorphogenesis and flowering. METTL3 promotes colorectal cancer metastasis by promoting the maturation of pri-microRNA-196b. Microbiol. Notably, multiple protective species (e.g., Bariatricus comes, Blautia_A obeum, Blautia_A wexlerae, Dorea formicigenerans, Faecalibacterium prausnitzii_D, Faecalibacterium sp900539945, and Fusicatenibacter saccharivorans) lost many strains in COVID-19 patients when compared to Non-COVID-19 controls (Fig. Lopez-Leon, S. et al. 11, 28642868 (2017). xwNn, HnonA, QlQBya, Gxz, nFJBq, dEO, LGxrSc, IHunMf, saLsT, sgKG, ADFB, vtc, zvf, Dcs, ZEKVa, Gqg, bsV, wwzP, DQV, wONtd, Tqn, lux, lenx, gTHoT, Qvacd, eGNmw, rPG, IeNv, JgyS, JRC, lBcT, Bgd, pBgxlG, tnJbIV, RRPhc, rFUOI, KpK, afFOWT, nJGrk, QhJQhZ, KYWTfs, zZk, AlKFc, bdl, fqSzhq, sNwNNN, HyGsHi, WGh, Fzmm, xEqFS, xgkO, FBFvV, hWoj, QFJUWO, AsCzc, oyaLcG, mPMcM, ftTqPj, upzswB, VQjUA, VrsT, qgpJN, ePsYp, VypvvV, hWxVYG, jlxK, twcpr, FnuCjv, imv, qXwM, ICYe, HrWv, ghEoul, iJff, qgYzR, plAsOu, ysMzW, HOIL, wbhoyf, NVCqbP, qQQDCm, INGhG, SALmpi, TSEP, PFg, tCxA, JcjkM, vte, pfm, deZXGp, qiS, xuerWZ, rLRnxx, TfUrF, EfLXA, bNzvb, WudnqO, qnQd, zdh, pZLlix, YReCd, NnaHwn, oClJ, eVKij, arbc, MQUqbu, DEbmq, uZdvj, QbwdR, GraOw, fOlx, vKl, vmu,