Featured Publications
Mapping subcellular localizations of unannotated microproteins and alternative proteins with MicroID
Na Z, Dai X, Zheng SJ, Bryant CJ, Loh KH, Su H, Luo Y, Buhagiar AF, Cao X, Baserga SJ, Chen S, Slavoff SA. Mapping subcellular localizations of unannotated microproteins and alternative proteins with MicroID. Molecular Cell 2022, 82: 2900-2911.e7. PMID: 35905735, PMCID: PMC9662605, DOI: 10.1016/j.molcel.2022.06.035.Peer-Reviewed Original ResearchConceptsSubcellular localizationProximity biotinylationSmall open reading framesAlternative proteinsOpen reading frameHigh-throughput technologiesSubnuclear organellesCanonical proteinsRRNA transcriptionSubcellular compartmentsReading frameProteogenomic identificationProtein compositionAmino acidsMicroproteinsProteinBiotinylationLocalizationTurboIDTranscriptionOrganellesMouse modelPolypeptideNucleoliExpressionAlt-RPL36 downregulates the PI3K-AKT-mTOR signaling pathway by interacting with TMEM24
Cao X, Khitun A, Luo Y, Na Z, Phoodokmai T, Sappakhaw K, Olatunji E, Uttamapinant C, Slavoff SA. Alt-RPL36 downregulates the PI3K-AKT-mTOR signaling pathway by interacting with TMEM24. Nature Communications 2021, 12: 508. PMID: 33479206, PMCID: PMC7820019, DOI: 10.1038/s41467-020-20841-6.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAmino Acid SequenceBase SequenceBiological TransportCell MembraneDown-RegulationEndoplasmic ReticulumHEK293 CellsHumansMembrane ProteinsMutationPhosphatidylinositol 3-KinasesPhosphatidylinositol 4,5-DiphosphateProtein BindingProto-Oncogene Proteins c-aktRibosomal ProteinsSignal TransductionTOR Serine-Threonine KinasesConceptsPI3K-AktEndoplasmic reticulumMTOR signalingHuman gene functionAlternative open reading framesOpen reading framePI3K signalingDifferent molecular mechanismsCanonical proteinsGene functionCell sizeReading framePrecursor phosphatidylinositolPlasma membraneTMEM24Upstream regulatorMolecular mechanismsPhosphoserine residuesK signalingPoint mutationsSignalingPhosphatidylinositolProteinReticulumRPL36
2021
Phosphorylation of a Human Microprotein Promotes Dissociation of Biomolecular Condensates
Na Z, Luo Y, Cui DS, Khitun A, Smelyansky S, Loria JP, Slavoff SA. Phosphorylation of a Human Microprotein Promotes Dissociation of Biomolecular Condensates. Journal Of The American Chemical Society 2021, 143: 12675-12687. PMID: 34346674, PMCID: PMC8564862, DOI: 10.1021/jacs.1c05386.Peer-Reviewed Original ResearchConceptsMembraneless organellesSmall open reading framesP-body dynamicsLiquid-liquid phase separationOpen reading frameGrowth factor signalingPresence of RNAEvolutionary conservationP-bodiesCellular processesCell divisionReading frameProteogenomic identificationFactor signalingMacromolecular complexesBiomolecular condensatesSecondary structureAmino acidsCell growthMicroproteinsPhosphorylationCell proliferationOrganellesBiophysical processesProliferation
2020
The NBDY Microprotein Regulates Cellular RNA Decapping
Na Z, Luo Y, Schofield JA, Smelyansky S, Khitun A, Muthukumar S, Valkov E, Simon MD, Slavoff SA. The NBDY Microprotein Regulates Cellular RNA Decapping. Biochemistry 2020, 59: 4131-4142. PMID: 33059440, PMCID: PMC7682656, DOI: 10.1021/acs.biochem.0c00672.Peer-Reviewed Original ResearchConceptsP-bodiesNonsense-mediated decay factorsKO cellsSmall open reading framesCytoplasmic ribonucleoprotein granulesOpen reading frameSubstrate transcriptsCellular transcriptomeRibonucleoprotein granulesTarget transcriptsRNA stabilityKnockout cellsUTR lengthReading frameGlobal profilingProteogenomic identificationMacromolecular complexesHuman RNACellular RNACytoplasmic RNAGene stabilityAmino acidsCell growthMicroproteinsTranscriptsComparative Proteomic Profiling of Unannotated Microproteins and Alternative Proteins in Human Cell Lines
Cao X, Khitun A, Na Z, Dumitrescu DG, Kubica M, Olatunji E, Slavoff SA. Comparative Proteomic Profiling of Unannotated Microproteins and Alternative Proteins in Human Cell Lines. Journal Of Proteome Research 2020, 19: 3418-3426. PMID: 32449352, PMCID: PMC7429271, DOI: 10.1021/acs.jproteome.0c00254.Peer-Reviewed Original ResearchConceptsRibosome profilingHuman cell linesQuantitative mass spectrometry-based proteomicsCell linesMass spectrometry-based proteomicsLabel-free quantitative proteomicsComplex human proteomeLabel-free comparative proteomicsAlternative open reading framesStress-dependent expressionSpectrometry-based proteomicsTissue-specific expressionOpen reading frameComparative proteomic profilingUnannotated ORFsComparative proteomicsUnannotated proteinsMammalian cellsHuman proteomeQuantitative proteomicsDifferential translationReading frameProteomic profilingHuman leukemia cell linesRegulated expressionNon-AUG start codons: Expanding and regulating the small and alternative ORFeome
Cao X, Slavoff SA. Non-AUG start codons: Expanding and regulating the small and alternative ORFeome. Experimental Cell Research 2020, 391: 111973. PMID: 32209305, PMCID: PMC7256928, DOI: 10.1016/j.yexcr.2020.111973.Peer-Reviewed Original ResearchConceptsSmall open reading framesFunctional small open reading framesStart codonClasses of genesImportant biological processesNon-AUG start codonsOpen reading frameNon-AUG codonsStart codon usageAUG start codonEukaryotic genomesGenomic toolsRibosome profilingNovel genesCodon usageReading frameProteomic studiesBiological processesSequence propertiesCodonGenesPresence of thousandsEukaryotesProkaryotes
2019
Proteomic Detection and Validation of Translated Small Open Reading Frames
Khitun A, Slavoff SA. Proteomic Detection and Validation of Translated Small Open Reading Frames. Current Protocols In Chemical Biology 2019, 11: e77. PMID: 31750990, PMCID: PMC6878975, DOI: 10.1002/cpch.77.Peer-Reviewed Original ResearchConceptsSiRNA-based silencingSmall open reading framesNon-AUG start codonsOpen reading frameStandard proteomic methodsSpecific transcript isoformsCultured human cellsUnique tryptic peptidesGenomic lociShorter proteinTranscript isoformsProtein databaseProteomic methodsNovel regulatorReading frameProteomic detectionStart codonFunctional characterizationMass spectrometry-based detectionComplete annotationSmall proteinsHuman cellsTryptic peptidesProtein extractionSmORFsSmall open reading frames and cellular stress responses
Khitun A, Ness TJ, Slavoff SA. Small open reading frames and cellular stress responses. Molecular Omics 2019, 15: 108-116. PMID: 30810554, PMCID: PMC6662920, DOI: 10.1039/c8mo00283e.Peer-Reviewed Original ResearchConceptsSmall open reading framesOpen reading frameUpstream ORFsReading frameStress responseCellular stress responseEukaryotic cellsGenome annotationCellular homeostasisDownstream cistronEvolutionary spaceFunctional polypeptidesAmino acidsEukaryotesSmORFsPolypeptideProkaryotesGenomeCistronGenomicsORFRecent advancesProteomicsFootprintingRegulator
2018
The translation of non-canonical open reading frames controls mucosal immunity
Jackson R, Kroehling L, Khitun A, Bailis W, Jarret A, York AG, Khan OM, Brewer JR, Skadow MH, Duizer C, Harman CCD, Chang L, Bielecki P, Solis AG, Steach HR, Slavoff S, Flavell RA. The translation of non-canonical open reading frames controls mucosal immunity. Nature 2018, 564: 434-438. PMID: 30542152, PMCID: PMC6939389, DOI: 10.1038/s41586-018-0794-7.Peer-Reviewed Original ResearchConceptsNon-canonical open reading framesOpen reading frameProtein-coding genomeReading frameNew open reading framesProtein-coding genesNon-protein codingNon-coding RNAsUnbiased transcriptomics approachTranscriptomic approachMethionine codonDistinct proteinsFunctional proteinsImportant transcriptsEssential roleGenomeAbsolute requirementGenesRNABacterial infectionsProteinaceous productsProteinTranslationMisannotationsCodon
2017
Comparative Membrane Proteomics Reveals a Nonannotated E. coli Heat Shock Protein
Yuan P, D’Lima N, Slavoff SA. Comparative Membrane Proteomics Reveals a Nonannotated E. coli Heat Shock Protein. Biochemistry 2017, 57: 56-60. PMID: 29039649, PMCID: PMC5761644, DOI: 10.1021/acs.biochem.7b00864.Peer-Reviewed Original ResearchMeSH KeywordsChromatography, High Pressure LiquidEscherichia coliEscherichia coli K12Escherichia coli ProteinsGene Expression Regulation, BacterialGreen Fluorescent ProteinsHeat-Shock ProteinsHeat-Shock Proteins, SmallHeat-Shock ResponseMembrane ProteinsModels, MolecularMolecular Sequence AnnotationOpen Reading FramesPhosphogluconate DehydrogenaseProtein Conformation, alpha-HelicalProtein Interaction Domains and MotifsProtein TransportProteogenomicsProteomicsRecombinant Fusion ProteinsTandem Mass SpectrometryConceptsHeat shock proteinsShock proteinsMembrane proteomicsE. coli heat shock proteinsComparative membrane proteomicsSmall open reading framesMembrane protein enrichmentQuantitative membrane proteomicsQuantitative proteomics protocolBacterial stress responseQuantitative mass spectrometryOpen reading frameDiscovery of thousandsEscherichia coli K12Transmembrane helicesProteomics protocolMembrane proteinsEvolutionary spaceReading frameSmall proteinsStress responseProteomicsColi K12Amino acidsProtein enrichmentComparative Proteomics Enables Identification of Nonannotated Cold Shock Proteins in E. coli
D’Lima N, Khitun A, Rosenbloom AD, Yuan P, Gassaway BM, Barber KW, Rinehart J, Slavoff SA. Comparative Proteomics Enables Identification of Nonannotated Cold Shock Proteins in E. coli. Journal Of Proteome Research 2017, 16: 3722-3731. PMID: 28861998, PMCID: PMC5647875, DOI: 10.1021/acs.jproteome.7b00419.Peer-Reviewed Original ResearchConceptsCold shock proteinsComparative proteomicsShock proteinsRelated Gram-negative bacteriaMass spectrometry-based proteomicsSmall open reading framesMolecular genetic approachesWhole genome databaseSpectrometry-based proteomicsOpen reading frameE. coliEukaryotic genomesGram-negative bacteriaCellular functionsDifferent organismsGenetic approachesReading frameBiological roleProteomicsMicroproteinsEnable identificationProteinColiGenomeRecent advances
2015
The Discovery of Human sORF‐Encoded Polypeptides (SEPs) in Cell Lines and Tissue
Ma J, Ward C, Jungreis I, Slavoff S, Schwaid A, Neveu J, Budnik B, Kellis M, Saghatelian A. The Discovery of Human sORF‐Encoded Polypeptides (SEPs) in Cell Lines and Tissue. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.567.21.Peer-Reviewed Original ResearchShort open reading framesNon-AUG start codonsOpen reading frameCell linesHuman genomeMammalian cellsReading frameStart codonAdditional cell linesPolypeptide productsMolecular biologyUbiquitous classK562 cellsGenomeProteomeHuman SEPsPolypeptideHuman tissuesNew SEPCellsCodonDiscoveryBiologyTissueLines
2014
A Human Short Open Reading Frame (sORF)-encoded Polypeptide That Stimulates DNA End Joining*
Slavoff SA, Heo J, Budnik BA, Hanakahi LA, Saghatelian A. A Human Short Open Reading Frame (sORF)-encoded Polypeptide That Stimulates DNA End Joining*. Journal Of Biological Chemistry 2014, 289: 10950-10957. PMID: 24610814, PMCID: PMC4036235, DOI: 10.1074/jbc.c113.533968.Peer-Reviewed Original ResearchDiscovery of Human sORF-Encoded Polypeptides (SEPs) in Cell Lines and Tissue
Ma J, Ward CC, Jungreis I, Slavoff SA, Schwaid AG, Neveu J, Budnik BA, Kellis M, Saghatelian A. Discovery of Human sORF-Encoded Polypeptides (SEPs) in Cell Lines and Tissue. Journal Of Proteome Research 2014, 13: 1757-1765. PMID: 24490786, PMCID: PMC3993966, DOI: 10.1021/pr401280w.Peer-Reviewed Original ResearchConceptsShort open reading framesNon-AUG start codonsOpen reading frameCell linesHuman genomeMammalian cellsReading frameStart codonAdditional cell linesPolypeptide productsMolecular biologyUbiquitous classK562 cellsGenomeProteomeHuman SEPsPolypeptideHuman tissuesNew SEPCellsCodonDiscoveryBiologyTissueLines
2013
Chemoproteomic Discovery of Cysteine-Containing Human Short Open Reading Frames
Schwaid AG, Shannon DA, Ma J, Slavoff SA, Levin JZ, Weerapana E, Saghatelian A. Chemoproteomic Discovery of Cysteine-Containing Human Short Open Reading Frames. Journal Of The American Chemical Society 2013, 135: 16750-16753. PMID: 24152191, PMCID: PMC3868496, DOI: 10.1021/ja406606j.Peer-Reviewed Original ResearchConceptsShort open reading framesOpen reading frameReading frameProtein-coding genesProtein-coding potentialGene-finding algorithmsAffinity-based approachRibosome profilingNew genesHuman proteomeMass spectrometry technologyEndogenous RNASpectrometry technologyLabeling approachGenesHuman SEPsPotential importanceInvaluable insightsExperimental approachGenomeProteomeDiscoveryRNABiologyPolypeptide