2022
Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC
Swartzel JC, Bond MJ, Pintado-Urbanc AP, Daftary M, Krone MW, Douglas T, Carder EJ, Zimmer JT, Maeda T, Simon MD, Crews CM. Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC. ACS Chemical Biology 2022, 17: 1789-1798. PMID: 35749470, PMCID: PMC10367122, DOI: 10.1021/acschembio.2c00145.Peer-Reviewed Original Research
2021
Hyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression
Rosa-Mercado NA, Zimmer JT, Apostolidi M, Rinehart J, Simon MD, Steitz JA. Hyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression. Molecular Cell 2021, 81: 502-513.e4. PMID: 33400923, PMCID: PMC7867636, DOI: 10.1016/j.molcel.2020.12.002.Peer-Reviewed Original ResearchConceptsWidespread transcriptional repressionTranscriptional repressionPol IIIntegrator complex subunitsRNA polymerase IIGenome-wide lossStress-induced redistributionParental genesTranscriptional outputDoG inductionPolymerase IIChIP sequencingHuman cell linesUpstream geneComplex subunitsPolyadenylation factorsTranscription profilesReadthrough transcriptsCatalytic subunitIntegrator activityCellular stressHyperosmotic stressTranscriptional levelTranscription resultsGenes
2020
Discovery of cellular substrates of human RNA-decapping enzyme DCP2 using a stapled bicyclic peptide inhibitor
Luo Y, Schofield JA, Na Z, Hann T, Simon MD, Slavoff SA. Discovery of cellular substrates of human RNA-decapping enzyme DCP2 using a stapled bicyclic peptide inhibitor. Cell Chemical Biology 2020, 28: 463-474.e7. PMID: 33357462, PMCID: PMC8052284, DOI: 10.1016/j.chembiol.2020.12.003.Peer-Reviewed Original ResearchMeSH KeywordsBridged Bicyclo Compounds, HeterocyclicDrug DiscoveryEndoribonucleasesEnzyme InhibitorsHEK293 CellsHumansMolecular ConformationPeptidesConceptsRNA decayEnzyme DCP2P-bodiesDCP2Genetic approachesRNA substratesBicyclic peptide inhibitorsHuman RNAExpression changesCellular substratesPhage display selectionSelective chemical inhibitorsChemical inhibitorsHuman cellsGenetic ablationBicyclic peptide ligandsPeptide inhibitorCP21Display selectionPeptide ligandsHigh affinityRegulomeTranscriptionInhibitorsPowerful tool