2024
Autonomous transposons tune their sequences to ensure somatic suppression
Ilık İ, Glažar P, Tse K, Brändl B, Meierhofer D, Müller F, Smith Z, Aktaş T. Autonomous transposons tune their sequences to ensure somatic suppression. Nature 2024, 626: 1116-1124. PMID: 38355802, PMCID: PMC10901741, DOI: 10.1038/s41586-024-07081-0.Peer-Reviewed Original ResearchConceptsTransposable elementsSAFB proteinsPiwi-interacting RNA pathwayRNA-basedIntronic transposed elementsRNA processing signalsPre-mRNA processingIntronic spaceNested genesPostmeiotic spermatidsAutonomous transposonsDNA transposonsRNA pathwaysCassette exonsSplicing codeSplicing eventsGenome integrityTE exonizationHuman genesL1 elementsRNA synthesisHost genesTissue-specificSAFBSomatic cells
2023
DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner
Strine M, Cai W, Wei J, Alfajaro M, Filler R, Biering S, Sarnik S, Chow R, Patil A, Cervantes K, Collings C, DeWeirdt P, Hanna R, Schofield K, Hulme C, Konermann S, Doench J, Hsu P, Kadoch C, Yan Q, Wilen C. DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner. PLOS Biology 2023, 21: e3002097. PMID: 37310920, PMCID: PMC10263356, DOI: 10.1371/journal.pbio.3002097.Peer-Reviewed Original ResearchConceptsGenome-wide CRISPR/Cas9 screenCRISPR/Cas9 screenPathogenic human coronavirusesKinase-independent mannerRegulated kinase 1AProviral host factorNovel drug targetsMultiple cell typesDNA accessibilityHost factorsKinase functionHuman coronavirusesHost genesDistal enhancerNovel regulatorCas9 screenKinase 1AGene expressionNeuronal developmentDYRK1ADrug targetsDiverse coronavirusesProviral activityCell typesSevere acute respiratory syndrome coronavirus 2
2022
Host gene effects on gut microbiota in type 1 diabetes
Guo K, Huang J, Zhou Z. Host gene effects on gut microbiota in type 1 diabetes. Biochemical Society Transactions 2022, 50: 1133-1142. PMID: 35521897, PMCID: PMC9246325, DOI: 10.1042/bst20220004.Peer-Reviewed Original ResearchConceptsType 1 diabetesMicrobiome compositionPancreatic β-cell lossT1D susceptibility genesT1D developmentHost genesImmunity genesGenetic lociGut microbiotaGene effectsModel of T1DNon-obese diabetic (NOD) miceOrgan-specific autoimmune diseasesΒ-cell lossGenesSusceptibility genesGenetic backgroundGenetic variantsMicrobiota interactionsRisk of T1DPancreatic islet autoantigensGut microbiota diversityGut microbiome compositionIslet autoimmunityT1D progression
2021
SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes
Pawlica P, Yario TA, White S, Wang J, Moss WN, Hui P, Vinetz JM, Steitz JA. SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2116668118. PMID: 34903581, PMCID: PMC8719879, DOI: 10.1073/pnas.2116668118.Peer-Reviewed Original ResearchConceptsBasic leucine zipper ATF-like transcription factor 2Small RNAsHuman lung-derived cell linesSARS-CoV-2 infectionLung-derived cell linesRNA interference (RNAi) pathwayHost miRNA levelsTranscription factor 2Cellular machineryInterference pathwayDrosha proteinSARS-CoV-2-infected individualsHost genesSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Host miRNAsPutative targetsSyndrome coronavirus 2SARS-CoV-2MiRNA levelsFactor 2Cell linesNasopharyngeal swabsCoronavirus 2
2020
Cytidine Monophosphate N-Acetylneuraminic Acid Synthetase and Solute Carrier Family 35 Member A1 Are Required for Reovirus Binding and Infection
Urbanek K, Sutherland DM, Orchard RC, Wilen CB, Knowlton JJ, Aravamudhan P, Taylor GM, Virgin HW, Dermody TS. Cytidine Monophosphate N-Acetylneuraminic Acid Synthetase and Solute Carrier Family 35 Member A1 Are Required for Reovirus Binding and Infection. Journal Of Virology 2020, 95: 10.1128/jvi.01571-20. PMID: 33087464, PMCID: PMC7944449, DOI: 10.1128/jvi.01571-20.Peer-Reviewed Original ResearchConceptsSialic acid expressionMicroglial cellsCell surface expressionReovirus-induced cell deathReovirus infectionSialic acidMurine microglial BV2 cellsReovirus-induced diseaseMember A1Microglial BV2 cellsSurface expressionMurine microglial cellsCell deathReovirus bindingBV2 cellsViral tropismInfectionHost genesLow-level bindingCell surface receptorsHost factorsCell surfaceReceptorsSialic acid synthesisSurface receptorsGenome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection
Wei J, Alfajaro MM, DeWeirdt PC, Hanna RE, Lu-Culligan WJ, Cai WL, Strine MS, Zhang SM, Graziano VR, Schmitz CO, Chen JS, Mankowski MC, Filler RB, Ravindra NG, Gasque V, de Miguel FJ, Patil A, Chen H, Oguntuyo KY, Abriola L, Surovtseva YV, Orchard RC, Lee B, Lindenbach BD, Politi K, van Dijk D, Kadoch C, Simon MD, Yan Q, Doench JG, Wilen CB. Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection. Cell 2020, 184: 76-91.e13. PMID: 33147444, PMCID: PMC7574718, DOI: 10.1016/j.cell.2020.10.028.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsCell LineChlorocebus aethiopsClustered Regularly Interspaced Short Palindromic RepeatsCoronavirusCoronavirus InfectionsCOVID-19Gene Knockout TechniquesGene Regulatory NetworksGenome-Wide Association StudyHEK293 CellsHMGB1 ProteinHost-Pathogen InteractionsHumansSARS-CoV-2Vero CellsVirus InternalizationConceptsSARS-CoV-2 infectionSARS-CoV-2Vesicular stomatitis virusGenome-wide CRISPR screenSWI/SNF chromatinSARS-CoV-2 host factorsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionTherapeutic targetHost factorsCoronavirus disease 2019 (COVID-19) pathogenesisSyndrome coronavirus 2 infectionCRISPR screensHost genesGene productsMiddle East respiratory syndrome CoVCoronavirus 2 infectionGenetic hitsHuman cellsSARS-CoV-2 spikeNovel therapeutic targetPotential therapeutic targetVero E6 cellsSARS-CoV-1Small molecule antagonists
2017
MiRIAD update: using alternative polyadenylation, protein interaction network analysis and additional species to enhance exploration of the role of intragenic miRNAs and their host genes
Hinske L, dos Santos F, Ohara D, Ohno-Machado L, Kreth S, Galante P. MiRIAD update: using alternative polyadenylation, protein interaction network analysis and additional species to enhance exploration of the role of intragenic miRNAs and their host genes. Database 2017, 2017: bax053. PMID: 29220447, PMCID: PMC5569676, DOI: 10.1093/database/bax053.Peer-Reviewed Original Research
2016
Epigenome-wide differential DNA methylation between HIV-infected and uninfected individuals
Zhang X, Justice AC, Hu Y, Wang Z, Zhao H, Wang G, Johnson EO, Emu B, Sutton RE, Krystal JH, Xu K. Epigenome-wide differential DNA methylation between HIV-infected and uninfected individuals. Epigenetics 2016, 11: 750-760. PMID: 27672717, PMCID: PMC5094631, DOI: 10.1080/15592294.2016.1221569.Peer-Reviewed Original ResearchDifferential DNA methylationDNA methylationLarge-scale epigenome-wide association studyMajor histocompatibility complex (MHC) class I gene expressionNovel host genesEpigenome-wide association studiesClass I gene expressionVeterans Aging Cohort StudyEpigenome-wide significant CpGsEpigenetic controlHIV-1 infectionHost genesI gene expressionEpigenetic changesHost genomeCARD domainKey regulatorGene expressionAssociation studiesSignificant CpGsGene 5CpG sitesMethylationCell typesLower methylationSREBP-1c/MicroRNA 33b Genomic Loci Control Adipocyte Differentiation
Price NL, Holtrup B, Kwei SL, Wabitsch M, Rodeheffer M, Bianchini L, Suárez Y, Fernández-Hernando C. SREBP-1c/MicroRNA 33b Genomic Loci Control Adipocyte Differentiation. Molecular And Cellular Biology 2016, 36: 1180-1193. PMID: 26830228, PMCID: PMC4800797, DOI: 10.1128/mcb.00745-15.Peer-Reviewed Original ResearchConceptsWhite adipose tissueCyclin-dependent kinase 6MiR-33bSREBP-1Adipocyte differentiationReceptor-γ target genesPeroxisome proliferator-activated receptor-γ target genesDevelopment of obesityStandard mouse modelSterol regulatory element-binding protein 2Lipid droplet formationLipid droplet accumulationIntronic microRNAsHost genesTarget genesMouse modelKinase 6Adipose tissueMetabolic diseasesNovel roleImportant regulatorHuman preadipocytesDroplet accumulationVivo assessmentProtein 2
2015
Alternative Polyadenylation Allows Differential Negative Feedback of Human miRNA miR-579 on Its Host Gene ZFR
Hinske L, Galante P, Limbeck E, Möhnle P, Parmigiani R, Ohno-Machado L, Camargo A, Kreth S. Alternative Polyadenylation Allows Differential Negative Feedback of Human miRNA miR-579 on Its Host Gene ZFR. PLOS ONE 2015, 10: e0121507. PMID: 25799583, PMCID: PMC4370670, DOI: 10.1371/journal.pone.0121507.Peer-Reviewed Original ResearchConceptsHost genesAlternative polyadenylationIntronic miRNAsMiR-579Protein-coding host genesPotential miRNA binding sitesHost gene expressionMiRNA binding sitesIntronic miRNAMiRNA genesNegative feedback loopRNA-seqPolyadenylation signalPolyadenylation sitesBioinformatics analysisCell line modelsGene expressionSilico analysisDifferential targetingPolyadenylationGenesMiRNAsZFRBinding sitesNegative feedback
2014
Autoregulation of glypican-1 by intronic microRNA-149 fine tunes the angiogenic response to FGF2 in human endothelial cells
Chamorro-Jorganes A, Araldi E, Rotllan N, Cirera-Salinas D, Suárez Y. Autoregulation of glypican-1 by intronic microRNA-149 fine tunes the angiogenic response to FGF2 in human endothelial cells. Journal Of Cell Science 2014, 127: 1169-1178. PMID: 24463821, PMCID: PMC3953812, DOI: 10.1242/jcs.130518.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, Lewis LungCells, CulturedFibroblast Growth Factor 2Gene ExpressionGlypicansHuman Umbilical Vein Endothelial CellsHumansMaleMiceMicroRNAsNeoplasm TransplantationNeovascularization, PathologicNeovascularization, PhysiologicReceptor, Fibroblast Growth Factor, Type 1RNA InterferenceSignal TransductionmiRIAD—integrating microRNA inter- and intragenic data
Hinske L, França G, Torres H, Ohara D, Lopes-Ramos C, Heyn J, Reis L, Ohno-Machado L, Kreth S, Galante P. miRIAD—integrating microRNA inter- and intragenic data. Database 2014, 2014: bau099. PMID: 25288656, PMCID: PMC4186326, DOI: 10.1093/database/bau099.Peer-Reviewed Original ResearchConceptsProtein-coding genesIntragenic miRNAsHost genesGene expressionProtein-protein interaction dataSmall non-coding RNAsHost gene functionHost gene expressionMiRNA binding sitesNon-coding RNAsMajority of miRNAsGene functionGenomic contextFunctional annotationFunctional network analysisTarget mRNAsExpression correlationExonic regionsGenesMiRNAsDifferent tissuesInteraction dataBinding sitesGenomic classificationSilico validation
2013
The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis
Liu M, Roth A, Yu M, Morris R, Bersani F, Rivera MN, Lu J, Shioda T, Vasudevan S, Ramaswamy S, Maheswaran S, Diederichs S, Haber DA. The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis. Genes & Development 2013, 27: 2543-2548. PMID: 24298054, PMCID: PMC3861668, DOI: 10.1101/gad.224170.113.Peer-Reviewed Original ResearchConceptsInsulin-like growth factor 2Loss of imprintingUntranslated regionFunctional positive feedback loopRNA helicase DHX9IGF2 mRNAAdditional regulatory mechanismsIntronic miRNANuclear poolHost genesEctopic expressionMicroRNA screenPositive feedback loopIGF2 transcriptionPrimary Wilms tumorsFetal promotersIGF2 transcriptsPromoter contributesRegulatory mechanismsIGF2 geneGrowth factor 2IGF2 expressionTranscriptionGenesMiR-483AID downregulation is a novel function of the DNMT inhibitor 5-aza-deoxycytidine
Tsai CT, Yang PM, Chern TR, Chuang SH, Lin JH, Klemm L, Müschen M, Chen CC. AID downregulation is a novel function of the DNMT inhibitor 5-aza-deoxycytidine. Oncotarget 2013, 5: 211-223. PMID: 24457556, PMCID: PMC3960202, DOI: 10.18632/oncotarget.1319.Peer-Reviewed Original ResearchConceptsActivation-induced cytidine deaminaseClass switch recombinationTumor suppressor geneHematopoietic cancer cellsAID expressionSomatic hypermutationNovel biological functionDNMT inhibitor 5Cancer cellsHost genesProteasomal degradationDNMT inhibitorsNovel functionBiological functionsInhibitor 5Suppressor geneSwitch recombinationImmunoglobulin genesCancer progressionCytidine deaminaseGenesDNMT1ZEBMolecular dockingActive siteSex-biased methylome and transcriptome in human prefrontal cortex
Xu H, Wang F, Liu Y, Yu Y, Gelernter J, Zhang H. Sex-biased methylome and transcriptome in human prefrontal cortex. Human Molecular Genetics 2013, 23: 1260-1270. PMID: 24163133, PMCID: PMC3919013, DOI: 10.1093/hmg/ddt516.Peer-Reviewed Original ResearchConceptsDNA methylationGene expressionSex-biased DNA methylationMultiple test correctionGenome-wide DNA methylationGene Ontology annotationsDAVID functional annotation analysisFunctional annotation analysisRibosome structurePhenotypic variationAnnotation analysisGO termsProtein translationRNA bindingOntology annotationsHost genesDifferential methylationExpression correlationTranscriptomic profilesDifferential brain developmentDifferential expressionMethylation levelsGenesMethylationTranscriptomeMicroRNA 33 Regulates Glucose Metabolism
Ramírez CM, Goedeke L, Rotllan N, Yoon JH, Cirera-Salinas D, Mattison JA, Suárez Y, de Cabo R, Gorospe M, Fernández-Hernando C. MicroRNA 33 Regulates Glucose Metabolism. Molecular And Cellular Biology 2013, 33: 2891-2902. PMID: 23716591, PMCID: PMC3719675, DOI: 10.1128/mcb.00016-13.Peer-Reviewed Original ResearchConceptsHost genesSterol regulatory element-binding protein (SREBP) genesSmall noncoding RNAsKey regulatory enzymeMiR-33bIntronic miRNAsHuman hepatic cellsMiR-33a/bPosttranscriptional regulationRegulatory genesExpression of PCK1Regulation of lipidNoncoding RNAsProtein geneG6pc expressionGene expressionBiological processesRegulatory enzymeMicroRNA-33GenesSpecific pathwaysMetabolic diseasesNovel therapeutic targetPhosphoenolpyruvate carboxykinaseRecent discoveryA Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression
Goedeke L, Vales-Lara FM, Fenstermaker M, Cirera-Salinas D, Chamorro-Jorganes A, Ramírez CM, Mattison JA, de Cabo R, Suárez Y, Fernández-Hernando C. A Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression. Molecular And Cellular Biology 2013, 33: 2339-2352. PMID: 23547260, PMCID: PMC3648071, DOI: 10.1128/mcb.01714-12.Peer-Reviewed Original ResearchConceptsMiR-33Gene expressionRegulatory roleTarget gene networkKey transcriptional regulatorTarget gene expressionMetabolism gene expressionIntronic microRNAsHuman hepatic cellsLipid metabolismSterol regulatory element-binding protein 2Transcriptional regulatorsSister strandsGene networksLipid metabolism gene expressionSteady-state levelsHost genesFatty acid metabolismFatty acid oxidationKey enzymeLipid homeostasisPassenger strandMicroRNA-33Functional roleProtein 2MicroRNAs in Metabolic Disease
Fernández-Hernando C, Ramírez CM, Goedeke L, Suárez Y. MicroRNAs in Metabolic Disease. Arteriosclerosis Thrombosis And Vascular Biology 2013, 33: 178-185. PMID: 23325474, PMCID: PMC3740757, DOI: 10.1161/atvbaha.112.300144.BooksConceptsContribution of miRNAsCellular cholesterol exportMiR-33Fatty acid degradationSREBP genesIntronic miRNAMetabolic diseasesFatty acid synthesisHost genesCholesterol exportSpecific miRNAsPhysiological processesLipid homeostasisMiRNAsAcid synthesisAcid degradationCardiometabolic diseasesGenesMicroRNAsGlucose homeostasisCritical roleGlucose metabolismLipoprotein secretionRecent findingsMetabolic control
2012
Human spliceosomal protein CWC22 plays a role in coupling splicing to exon junction complex deposition and nonsense-mediated decay
Alexandrov A, Colognori D, Shu MD, Steitz JA. Human spliceosomal protein CWC22 plays a role in coupling splicing to exon junction complex deposition and nonsense-mediated decay. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 21313-21318. PMID: 23236153, PMCID: PMC3535618, DOI: 10.1073/pnas.1219725110.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCarrier ProteinsEukaryotic Initiation Factor-4AEukaryotic Initiation Factor-4GExonsGene Knockdown TechniquesHEK293 CellsHeLa CellsHumansMolecular Sequence DataMutationNonsense Mediated mRNA DecayNuclear ProteinsPeptidylprolyl IsomeraseProtein BindingRNA SplicingRNA-Binding ProteinsRNA, MessengerSpliceosomesConceptsExon junction complexEJC depositionMultiprotein exon junction complexNonsense-mediated decay pathwayNonsense-mediated decaySpecific roleEJC assemblyEJC formationComplex eukaryotesDisrupts associationMetazoan mRNAsSpliceosomal proteinsCellular mRNAsHost genesSplicing defectsJunction complexDownstream eventsSplicingNatural substrateDecay pathwaysCWC22Depletion yieldsNMDMutationsMRNASome Novel Insights on HPV16 Related Cervical Cancer Pathogenesis Based on Analyses of LCR Methylation, Viral Load, E7 and E2/E4 Expressions
Ghosh D, Bhattacharjee B, Sen S, Premi L, Mukhopadhyay I, Chowdhury R, Roy S, Sengupta S. Some Novel Insights on HPV16 Related Cervical Cancer Pathogenesis Based on Analyses of LCR Methylation, Viral Load, E7 and E2/E4 Expressions. PLOS ONE 2012, 7: e44678. PMID: 22970286, PMCID: PMC3435323, DOI: 10.1371/journal.pone.0044678.Peer-Reviewed Original ResearchConceptsLong control regionViral loadViral genomeReplication originsCaCx casesEpisomal HPV16 genomesLack of methylationE7 mRNA expressionHuman papillomavirus 16Binding site IGene copy numberCervical cancer pathogenesisRepressor proteinBisulphite sequencingControl regionHPV16 genomeCervical carcinogenesisHost genesGenomeCervical cancerCopy numberViral transcriptionHPV16Cancer pathogenesisOncogene E7
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