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Karla M Neugebauer, PhD

Professor of Molecular Biophysics and Biochemistry and of Cell Biology; Director of Graduate Studies, Molecular Biophysics and Biochemistry; Director, Yale Center for RNA Science and Medicine

Research & Publications
Biography
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Research Summary

We are interested in links between in transcription and splicing, as well as the role of cellular subcompartments in RNA biogenesis. We use imaging, techniques that capture RNA-protein interactions, and next generation sequencing as major tools. We study these phenomena in yeast (fission and budding), zebrafish and mammalian tissue culture cells.

Specialized Terms: pre-mRNA splicing, transcription, gene architecture, SR proteins, cap-binding complex, RNA-protein interactions, Cajal bodies, organization of the cell nucleus, zebrafish embryogenesis.

Coauthors

Research Interests

Biochemistry; Biophysics; Cell Nucleus; Cell Biology; Molecular Biology; RNA Splicing; Saccharomyces cerevisiae; Schizosaccharomyces; Transcription, Genetic; Zebrafish; Alternative Splicing; Genomics; Nuclear Cap-Binding Protein Complex

Research Image

Higher order organization and functional links among gene expression machineries.

Illustration of the nucleus and cytoplasm of a eukaryotic cell containing nonmembrane-bound cellular bodies, such as nucleoli, Cajal bodies, the histone locus bodies, and P-bodies. Cellular bodies promote molecular interactions by increasing the local concentration of factors. They are often linked to transcription of particular genes (nucleolus: rDNA genes; CB: snRNA genes; histone body locus: histone genes). Similarly, individual machines are rich in RNA polymerase, spliceosomes, RNA-binding proteins and other factors that communicate with one another during gene regulation.

Selected Publications

U2AF1 Splicing Factor Mutations Affect RNA Subcellular Compartmentalization in Myeloid MalignanciesBiancon G, Busarello E, Lessard M, Courvan E, Escayola D, VanOudenhove J, Lee V, Krick M, Bewersdorf J, Neugebauer K, Tebaldi T, Halene S. U2AF1 Splicing Factor Mutations Affect RNA Subcellular Compartmentalization in Myeloid Malignancies Blood 2022, 140: 1271-1272. DOI: 10.1182/blood-2022-170043.
PYME: an integrated platform for high-throughput nanoscopyBarentine A, Lin Y, Courvan E, Kidd P, Liu M, Balduf L, Phan T, Rivera-Molina F, Grace M, Marin Z, Chen J, Wang S, Neugebauer K, Baddeley D, Bewersdorf J. PYME: an integrated platform for high-throughput nanoscopy Biophysical Journal 2022, 121: 137a. DOI: 10.1016/j.bpj.2021.11.2009.
U2AF1 Mutations Enhance Stress Granule Response in Myeloid MalignanciesBiancon G, Joshi P, Zimmer J, Hunck T, Gao Y, Lessard M, Courchaine E, Barentine A, Machyna M, Botti V, Qin A, Gbyli R, Patel A, Song Y, Kiefer L, Viero G, Neuenkirchen N, Lin H, Bewersdorf J, Simon M, Neugebauer K, Tebaldi T, Halene S. U2AF1 Mutations Enhance Stress Granule Response in Myeloid Malignancies Blood 2021, 138: 321-321. DOI: 10.1182/blood-2021-149618.
High-Resolution Binding Atlas of U2AF1 Mutants Uncovers New Complexity in Splicing Alterations and Kinetics in Myeloid MalignanciesBiancon G, Joshi P, Hunck T, Zimmer J, Gao Y, Machyna M, Botti V, Qin A, Viero G, Neuenkirchen N, Taylor A, Gbyli R, Patel A, Ardasheva A, Fu X, Lin H, Simon M, Neugebauer K, Tebaldi T, Halene S. High-Resolution Binding Atlas of U2AF1 Mutants Uncovers New Complexity in Splicing Alterations and Kinetics in Myeloid Malignancies Blood 2020, 136: 3-4. DOI: 10.1182/blood-2020-142854.
Contribution of increasing plasma membrane to the energetic cost of early zebrafish embryogenesisRodenfels J, Sartori P, Golfier S, Nagendra K, Neugebauer K, Howard J. Contribution of increasing plasma membrane to the energetic cost of early zebrafish embryogenesis Molecular Biology Of The Cell 2020, 31: 520-526. PMID: 32049586, PMCID: PMC7202076, DOI: 10.1091/mbc.e19-09-0529.
U2AF1 Driver Mutations in Hematopoietic Disorders Alter but Do Not Abrogate RNA Binding and Enlighten Structural Dependencies of the U2AF-RNA ComplexBiancon G, Joshi P, Hunck T, Gao Y, Botti V, Qin A, Sadykov M, Wang X, Viero G, Neuenkirchen N, Taylor A, Huang J, Ardasheva A, Fu X, Lin H, Pillai M, Kielkopf C, Neugebauer K, Tebaldi T, Halene S. U2AF1 Driver Mutations in Hematopoietic Disorders Alter but Do Not Abrogate RNA Binding and Enlighten Structural Dependencies of the U2AF-RNA Complex Blood 2019, 134: 1230-1230. DOI: 10.1182/blood-2019-130759.
Dynamics and Function of Nuclear Bodies during EmbryogenesisEscayola D, Neugebauer K. Dynamics and Function of Nuclear Bodies during Embryogenesis Biochemistry 2018, 57: 2462-2469. PMID: 29473743, DOI: 10.1021/acs.biochem.7b01262.
Are Cajal Bodies Droplet Organelles?Courchaine E, Neugebauer K. Are Cajal Bodies Droplet Organelles? Biophysical Journal 2018, 114: 440a. DOI: 10.1016/j.bpj.2017.11.2434.
Coupling between Transcription & Splicing Tunes Gene ExpressionNeugebauer K. Coupling between Transcription & Splicing Tunes Gene Expression Biophysical Journal 2018, 114: 366a. DOI: 10.1016/j.bpj.2017.11.2026.
Nuclear bodies: RNA‐rich powerhouses of the cell (471.3)Neugebauer K, Machyna M, Straube K, Heyn P. Nuclear bodies: RNA‐rich powerhouses of the cell (471.3) The FASEB Journal 2014, 28 DOI: 10.1096/fasebj.28.1_supplement.471.3.
Immunopurification of Endogenous RNAs Associated with RNA Binding Proteins In vivoÄnkö M, Neugebauer K. Immunopurification of Endogenous RNAs Associated with RNA Binding Proteins In vivo 2014, 1017-1028. DOI: 10.1002/9783527647064.ch45.
Transcription and Pre‐mRNA processing in space and timeNeugebauer K. Transcription and Pre‐mRNA processing in space and time The FASEB Journal 2012, 26: 228.2-228.2. DOI: 10.1096/fasebj.26.1_supplement.228.2.
Integration of Splicing with Nuclear and Cellular EventsSapra A, Neugebauer K. Integration of Splicing with Nuclear and Cellular Events 2012, 109-117. DOI: 10.1002/9783527636778.ch9.
Splicing Factor ChIP and ChRIP: Detection of Splicing and Splicing Factors at Genes by Chromatin ImmunoprecipitationSapra A, Oesterreich F, Pabis M, Listerman I, Bardehle N, Neugebauer K. Splicing Factor ChIP and ChRIP: Detection of Splicing and Splicing Factors at Genes by Chromatin Immunoprecipitation 2012, 416-427. DOI: 10.1002/9783527636778.ch39.
Co-transcriptional spliceosome assembly on mammalian model genesBardehle N, Neugebauer K. Co-transcriptional spliceosome assembly on mammalian model genes New Biotechnology 2010, 27: s33-s34. DOI: 10.1016/j.nbt.2010.01.039.
ReflectionsReichardt L, Tomaselli K, Neugebauer K, Bixby J, Lilien J, Reichardt L. Reflections Neuron 2008, 60: 398-399. PMID: 18995807, PMCID: PMC2623248, DOI: 10.1016/j.neuron.2008.10.030.
Fluorescent Detection of Nascent Transcripts and RNA‐binding Proteins in Cell NucleiGeiger J, Neugebauer K. Fluorescent Detection of Nascent Transcripts and RNA‐binding Proteins in Cell Nuclei 2005, 729-736. DOI: 10.1002/9783527619504.ch44.
SR proteins are autoantigens in patients with systemic lupus erythematosus: Importance of phosphoepitopesNeugebauer K, Merrill J, Wener M, Lahita R, Roth M. SR proteins are autoantigens in patients with systemic lupus erythematosus: Importance of phosphoepitopes Arthritis & Rheumatism 2000, 43: 1768-1778. PMID: 10943867, DOI: 10.1002/1529-0131(200008)43:8<1768::aid-anr13>3.0.co;2-9.
Regulation of Alternative Polyadenylation by U1 snRNPs and SRp20Lou H, Neugebauer K, Gagel R, Berget S. Regulation of Alternative Polyadenylation by U1 snRNPs and SRp20 Molecular And Cellular Biology 1998, 18: 4977-4985. PMID: 9710581, PMCID: PMC109082, DOI: 10.1128/mcb.18.9.4977.
Transcription units as RNA processing unitsNeugebauer K, Roth M. Transcription units as RNA processing units Genes & Development 1997, 11: 3279-3285. PMID: 9407022, DOI: 10.1101/gad.11.24.3279.
Distribution of pre-mRNA splicing factors at sites of RNA polymerase II transcription.Neugebauer K, Roth M. Distribution of pre-mRNA splicing factors at sites of RNA polymerase II transcription. Genes & Development 1997, 11: 1148-1159. PMID: 9159396, DOI: 10.1101/gad.11.9.1148.
A subset of SR proteins activates splicing of the cardiac troponin T alternative exon by direct interactions with an exonic enhancer.Ramchatesingh J, Zahler A, Neugebauer K, Roth M, Cooper T. A subset of SR proteins activates splicing of the cardiac troponin T alternative exon by direct interactions with an exonic enhancer. Molecular And Cellular Biology 1995, 15: 4898-4907. PMID: 7651409, PMCID: PMC230736, DOI: 10.1128/mcb.15.9.4898.
A conserved epitope on a subset of SR proteins defines a larger family of Pre-mRNA splicing factors.Neugebauer K, Stolk J, Roth M. A conserved epitope on a subset of SR proteins defines a larger family of Pre-mRNA splicing factors. Journal Of Cell Biology 1995, 129: 899-908. PMID: 7538140, PMCID: PMC2120486, DOI: 10.1083/jcb.129.4.899.
Human SR proteins and isolation of a cDNA encoding SRp75.Zahler A, Neugebauer K, Stolk J, Roth M. Human SR proteins and isolation of a cDNA encoding SRp75. Molecular And Cellular Biology 1993, 13: 4023-4028. PMID: 8321209, PMCID: PMC359951, DOI: 10.1128/mcb.13.7.4023.
Human SR proteins and isolation of a cDNA encoding SRp75Zahler A, Neugebauer K, Stolk J, Roth M. Human SR proteins and isolation of a cDNA encoding SRp75 Molecular And Cellular Biology 1993, 13: 4023-4028. DOI: 10.1128/mcb.13.7.4023-4028.1993.
Distinct Functions of SR Proteins in Alternative pre-mRNA SplicingZahler A, Neugebauer K, Lane W, Roth M. Distinct Functions of SR Proteins in Alternative pre-mRNA Splicing Science 1993, 260: 219-222. PMID: 8385799, DOI: 10.1126/science.8385799.
Adhesion of a chicken myeloblast cell line to fibrinogen and vitronectin through a beta 1-class integrin.Neugebauer K, Venstrom K, Reichardt L. Adhesion of a chicken myeloblast cell line to fibrinogen and vitronectin through a beta 1-class integrin. Journal Of Cell Biology 1992, 116: 809-815. PMID: 1370500, PMCID: PMC2289312, DOI: 10.1083/jcb.116.3.809.
Adhesive interactions that regulate development of the retina and primary visual projection.Reichardt L, Bossy B, de Curtis I, Neugebauer K, Venstrom K, Sretavan D. Adhesive interactions that regulate development of the retina and primary visual projection. Cold Spring Harbor Symposia On Quantitative Biology 1992, 57: 419-29. PMID: 1339677, DOI: 10.1101/sqb.1992.057.01.047.
2001 interactions? An extracellular space odysseyTomaselli K, Neugebauer K. 2001 interactions? An extracellular space odyssey Current Opinion In Neurobiology 1991, 1: 364-369. PMID: 1821678, DOI: 10.1016/0959-4388(91)90054-b.
Vitronectin and thrombospondin promote retinal neurite outgrowth: Developmental regulation and role of integrinsNeugebauer K, Emmett C, Venstrom K, Reichardt L. Vitronectin and thrombospondin promote retinal neurite outgrowth: Developmental regulation and role of integrins Neuron 1991, 6: 345-358. PMID: 1705807, DOI: 10.1016/0896-6273(91)90244-t.
Cell-surface regulation of β1-integrin activity on developing retinal neuronsNeugebauer K, Rekhardt L. Cell-surface regulation of β1-integrin activity on developing retinal neurons Nature 1991, 350: 68-71. PMID: 1706071, PMCID: PMC2710139, DOI: 10.1038/350068a0.
Neuronal receptors that regulate axon growth.Reichardt L, Bossy B, Carbonetto S, de Curtis I, Emmett C, Hall D, Ignatius M, Lefcort F, Napolitano E, Large T, Neugebauer K, Tomaselli K. Neuronal receptors that regulate axon growth. Cold Spring Harbor Symposia On Quantitative Biology 1990, 55: 341-50. PMID: 2132826, DOI: 10.1101/sqb.1990.055.01.035.
Integrins and Cell Adhesion Molecules: Neuronal Receptors That Regulate Axon Growth on Extracellular Matrices and Cell SurfacesReichardt L, Bixby J, Hall D, Ignatius M, Neugebauer K, Tomaselli K. Integrins and Cell Adhesion Molecules: Neuronal Receptors That Regulate Axon Growth on Extracellular Matrices and Cell Surfaces Developmental Neuroscience 1989, 11: 332-347. PMID: 2551626, DOI: 10.1159/000111910.
N-cadherin, NCAM, and integrins promote retinal neurite outgrowth on astrocytes in vitro.Neugebauer K, Tomaselli K, Lilien J, Reichardt L. N-cadherin, NCAM, and integrins promote retinal neurite outgrowth on astrocytes in vitro. Journal Of Cell Biology 1988, 107: 1177-1187. PMID: 3262111, PMCID: PMC2115273, DOI: 10.1083/jcb.107.3.1177.
N-cadherin and integrins: Two receptor systems that mediate neuronal process outgrowth on astrocyte surfacesTomaselli K, Neugebauer K, Bixby J, Lilien J, Reichard L. N-cadherin and integrins: Two receptor systems that mediate neuronal process outgrowth on astrocyte surfaces Neuron 1988, 1: 33-43. PMID: 2856086, DOI: 10.1016/0896-6273(88)90207-3.
Embryonic Chick Neural Retinal Cell Interactions with Extracellular Matrix Proteins: Characterization of Neuronal ECM Receptors and Changes in Receptor Activity During DevelopmentHall D, Neugebauer K, Reichardt L. Embryonic Chick Neural Retinal Cell Interactions with Extracellular Matrix Proteins: Characterization of Neuronal ECM Receptors and Changes in Receptor Activity During Development 1988, 151-170. DOI: 10.1007/978-1-4612-3920-8_9.
Embryonic neural retinal cell response to extracellular matrix proteins: developmental changes and effects of the cell substratum attachment antibody (CSAT).Hall D, Neugebauer K, Reichardt L. Embryonic neural retinal cell response to extracellular matrix proteins: developmental changes and effects of the cell substratum attachment antibody (CSAT). Journal Of Cell Biology 1987, 104: 623-634. PMID: 3493247, PMCID: PMC2114555, DOI: 10.1083/jcb.104.3.623.

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