2023
Impaired Early Spliceosome Complex Assembly Underlies Gene Body Elongation Transcription Defect in SF3B1K700E
Boddu P, Gupta A, Roy R, De La Pena Avalos B, Herrero A, Zimmer J, Simon M, Chandhok N, King D, Neuenkirchen N, Dray E, Lin H, Kupfer G, Verma A, Neugebauer K, Pillai M. Impaired Early Spliceosome Complex Assembly Underlies Gene Body Elongation Transcription Defect in SF3B1K700E. Blood 2023, 142: 714. DOI: 10.1182/blood-2023-187303.Peer-Reviewed Original ResearchSplicing factorsChIP-seqK562 cell lineKey regulatory genesCell linesSingle mutant alleleNon-denaturing gelsAlternative splicingTranscriptional kineticsRegulatory genesSpliceosome assemblySplicing efficiencyMRNA splicingCRISPR/Progenitor populationsNeomorphic functionsMolecular mechanismsMutant allelesIsoform changesGene editingNovel mechanismMutationsSF mutationsRecurrent mutationsAssembly kineticsTranscription Defects in SF3B1K700E Induce Targetable Alterations in the Chromatin Landscape
Boddu P, Gupta A, Roy R, Herrero A, Verma A, Neugebauer K, Pillai M. Transcription Defects in SF3B1K700E Induce Targetable Alterations in the Chromatin Landscape. Blood 2023, 142: 709. DOI: 10.1182/blood-2023-188083.Peer-Reviewed Original ResearchChromatin organizationSuch epigenetic changesGenome editing approachesRNA splicing factorsChromatin landscapeSingle mutant alleleEpigenetic landscapeGenomic integrityTranscription defectTranscription kineticsSplicing factorsChIP-seqEpigenetic regulatorsEpigenetic changesEpigenetic therapyMutant allelesEditing approachesFactor mutationsK562 cell lineDownstream effectsCell linesMyeloid disordersClonal myeloid disordersHDAC pathwayMutations
2020
Binding of FANCD2 to SRSF1 Splicing Factor Prevents Genomic Instability through R Loop Regulation
Olazabal-Herrero A, Green A, Chen X, Sung P, Pillai M, Kupfer G. Binding of FANCD2 to SRSF1 Splicing Factor Prevents Genomic Instability through R Loop Regulation. Blood 2020, 136: 19. DOI: 10.1182/blood-2020-141369.Peer-Reviewed Original ResearchR-loopsFA pathwayGenomic instabilityFanconi anemiaSplicing factorsR-loop metabolismR-loop regulationFA-like phenotypeBasic cellular processesR-loop formationKey regulatory stepNon-canonical roleDNA damaging agentsNon-canonical mechanismFANCD2-FANCIGenome maintenanceFANCD2 monoubiquitinationMRNA exportGenomic sitesCellular processesInsect cellsProcessing proteinsFA phenotypeRNA transcriptionRegulatory step
2013
Expression Of Mutant Spliceosomal Protein SF3B1 Results In Dysregulated Hematopoietic Maturation
Minella A, Ramirez O, Xu Y, Murthy T, Yang X, Pillai M. Expression Of Mutant Spliceosomal Protein SF3B1 Results In Dysregulated Hematopoietic Maturation. Blood 2013, 122: 2773. DOI: 10.1182/blood.v122.21.2773.2773.Peer-Reviewed Original ResearchSplicing of RNAErythroid maturationErythroid differentiationRNA splicing factorsMurine progenitor cellsMyelodysplastic syndromeWhole-genome sequencingSpliceosomal proteinsSplicing factorsColony forming assaysMutant SF3B1SF3B1 mutationsHematopoietic maturationCDNA constructsHuman cord bloodComplementary experimental approachesAddition of erythropoietinHematopoietic precursor cellsGenome sequencingMDS patientsMolecular mechanismsPosition 700Accessory receptorsHematopoietic progenitorsNormal hematopoiesis