Douglas Black*
We are interested in how cells process genetic information to form the messenger RNAs (mRNAs) that encode proteins, and our primary focus is the regulation of the pre-mRNA splicing reaction. In producing multiple mRNAs and proteins from a single DNA gene, alternative splicing is a key mechanism for creating the specialized functions of cells. This mode of gene regulation is particularly prevalent in the mammalian nervous system, where it contributes to the enormous diversity of neuronal cells. Errors in RNA splicing and its regulation also contribute to many aspects of human disease, including cancer, neurodegeneration, and inherited genetic disorders. In studying a variety of biological systems and applying a wide range of molecular approaches, our common goal is to develop a mechanistic understanding of gene regulation at the RNA level, and ultimately apply this knowledge to human health.
Websites:
Research Interests:
Posttranscriptional gene regulation in neurons, RNA metabolism in mammalian cells, Structure and function of RNA binding proteins and RNP complexes, regulation of pre-mRNA splicing,Publications:
Herrero-Vicente J, Black DL, Valcárcel J. Splice-modifying drug mechanisms. Nat Chem Biol. 2024 Sep; 20(9):1103-1105. view on PubMed
Peyda P, Lin CH, Onwuzurike K, Black DL. The Rbfox1/LASR complex controls alternative pre-mRNA splicing by recognition of multi-part RNA regulatory modules. bioRxiv. 2024 Jul 16. view on PubMed
Xiao W, Halabi R, Lin CH, Nazim M, Yeom KH, Black DL. The lncRNA Malat1 is trafficked to the cytoplasm as a localized mRNA encoding a small peptide in neurons. Genes Dev. 2024 05 21; 38(7-8):294-307. view on PubMed
Nazim M, Lin CH, Feng AC, Xiao W, Yeom KH, Li M, Daly AE, Tan X, Vu H, Ernst J, Carey MF, Smale ST, Black DL. Alternative splicing of a chromatin modifier alters the transcriptional regulatory programs of stem cell maintenance and neuronal differentiation. Cell Stem Cell. 2024 May 02; 31(5):754-771.e6. view on PubMed
Damianov A, Lin CH, Huang J, Zhou L, Jami-Alahmadi Y, Peyda P, Wohlschlegel J, Black DL. The splicing regulators RBM5 and RBM10 are subunits of the U2 snRNP engaged with intron branch sites on chromatin. Mol Cell. 2024 Apr 18; 84(8):1496-1511.e7. view on PubMed
Xiao W, Halabi R, Lin CH, Nazim M, Yeom KH, Black DL. The lncRNA Malat1 is trafficked to the cytoplasm as a localized mRNA encoding a small peptide in neurons. bioRxiv. 2024 Feb 01. view on PubMed
Tang AA, Afasizheva A, Cano CT, Plath K, Black D, Franco E. Optimization of RNA Pepper Sensors for the Detection of Arbitrary RNA Targets. ACS Synth Biol. 2024 02 16; 13(2):498-508. view on PubMed
Achiro JM, Tao Y, Gao F, Lin CH, Watanabe M, Neumann S, Coppola G, Black DL, Martin KC. Aging differentially alters the transcriptome and landscape of chromatin accessibility in the male and female mouse hippocampus. Front Mol Neurosci. 2024; 17:1334862. view on PubMed
Dror I, Chitiashvili T, Tan SYX, Cano CT, Sahakyan A, Markaki Y, Chronis C, Collier AJ, Deng W, Liang G, Sun Y, Afasizheva A, Miller J, Xiao W, Black DL, Ding F, Plath K. XIST directly regulates X-linked and autosomal genes in naive human pluripotent cells. Cell. 2024 01 04; 187(1):110-129.e31. view on PubMed
Damianov A, Lin CH, Huang J, Zhou L, Jami-Alahmadi Y, Wohlschlegel J, Black DL. The apoptotic splicing regulators RBM5 and RBM10 are subunits of the U2 snRNP engaged with intron branch sites on chromatin. bioRxiv. 2023 Sep 21. view on PubMed
Chen X, Yang HT, Zhang B, Phillips JW, Cheng D, Rigo F, Witte ON, Xing Y, Black DL. The RNA-binding proteins hnRNP H and F regulate splicing of a MYC-dependent HRAS exon in prostate cancer cells. Proc Natl Acad Sci U S A. 2023 07 11; 120(28):e2220190120. view on PubMed
Xiao W, Yeom KH, Lin CH, Black DL. Improved enzymatic labeling of fluorescent in situ hybridization probes applied to the visualization of retained introns in cells. RNA. 2023 08; 29(8):1274-1287. view on PubMed
Qian K, Tol MJ, Wu J, Uchiyama LF, Xiao X, Cui L, Bedard AH, Weston TA, Rajendran PS, Vergnes L, Shimanaka Y, Yin Y, Jami-Alahmadi Y, Cohn W, Bajar BT, Lin CH, Jin B, DeNardo LA, Black DL, Whitelegge JP, Wohlschlegel JA, Reue K, Shivkumar K, Chen FJ, Young SG, Li P, Tontonoz P. CLSTN3β enforces adipocyte multilocularity to facilitate lipid utilization. Nature. 2023 01; 613(7942):160-168. view on PubMed
Yeom KH, Pan Z, Lin CH, Lim HY, Xiao W, Xing Y, Black DL. Tracking pre-mRNA maturation across subcellular compartments identifies developmental gene regulation through intron retention and nuclear anchoring. Genome Res. 2021 06; 31(6):1106-1119. view on PubMed
Pandya-Jones A, Markaki Y, Serizay J, Chitiashvili T, Leon WRM, Damianov A, Chronis C, Papp B, Chen CK, McKee R, Wang XJ, Chau A, Sabri S, Leonhardt H, Zheng S, Guttman M, Black DL, Plath K. Publisher Correction: A protein assembly mediates Xist localization and gene silencing. Nature. 2020 Oct; 586(7830):E30. view on PubMed
Pandya-Jones A, Markaki Y, Serizay J, Chitiashvili T, Mancia Leon WR, Damianov A, Chronis C, Papp B, Chen CK, McKee R, Wang XJ, Chau A, Sabri S, Leonhardt H, Zheng S, Guttman M, Black DL, Plath K. A protein assembly mediates Xist localization and gene silencing. Nature. 2020 11; 587(7832):145-151. view on PubMed
Phillips JW, Pan Y, Tsai BL, Xie Z, Demirdjian L, Xiao W, Yang HT, Zhang Y, Lin CH, Cheng D, Hu Q, Liu S, Black DL, Witte ON, Xing Y. Pathway-guided analysis identifies Myc-dependent alternative pre-mRNA splicing in aggressive prostate cancers. Proc Natl Acad Sci U S A. 2020 03 10; 117(10):5269-5279. view on PubMed
Zhang Z, Pan Z, Ying Y, Xie Z, Adhikari S, Phillips J, Carstens RP, Black DL, Wu Y, Xing Y. Deep-learning augmented RNA-seq analysis of transcript splicing. Nat Methods. 2019 04; 16(4):307-310. view on PubMed
Cao Q, Shin WS, Chan H, Vuong CK, Dubois B, Li B, Murray KA, Sawaya MR, Feigon J, Black DL, Eisenberg DS, Jiang L. Author Correction: Inhibiting amyloid-β cytotoxicity through its interaction with the cell surface receptor LilrB2 by structure-based design. Nat Chem. 2018 12; 10(12):1267. view on PubMed
Yeom KH, Mitchell S, Linares AJ, Zheng S, Lin CH, Wang XJ, Hoffmann A, Black DL. Polypyrimidine tract-binding protein blocks miRNA-124 biogenesis to enforce its neuronal-specific expression in the mouse. Proc Natl Acad Sci U S A. 2018 11 20; 115(47):E11061-E11070. view on PubMed
Cao Q, Shin WS, Chan H, Vuong CK, Dubois B, Li B, Murray KA, Sawaya MR, Feigon J, Black DL, Eisenberg DS, Jiang L. Inhibiting amyloid-β cytotoxicity through its interaction with the cell surface receptor LilrB2 by structure-based design. Nat Chem. 2018 12; 10(12):1213-1221. view on PubMed
Vuong CK, Wei W, Lee JA, Lin CH, Damianov A, de la Torre-Ubieta L, Halabi R, Otis KO, Martin KC, O'Dell TJ, Black DL. Rbfox1 Regulates Synaptic Transmission through the Inhibitory Neuron-Specific vSNARE Vamp1. Neuron. 2018 04 04; 98(1):127-141.e7. view on PubMed
Li Q, Zheng S, Han A, Lin CH, Stoilov P, Fu XD, Black DL. Correction: The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation. Elife. 2017 10 09; 6. view on PubMed
Ying Y, Wang XJ, Vuong CK, Lin CH, Damianov A, Black DL. Splicing Activation by Rbfox Requires Self-Aggregation through Its Tyrosine-Rich Domain. Cell. 2017 Jul 13; 170(2):312-323.e10. view on PubMed
Ke S, Pandya-Jones A, Saito Y, Fak JJ, Vågbø CB, Geula S, Hanna JH, Black DL, Darnell JE, Darnell RB. m6A mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover. Genes Dev. 2017 05 15; 31(10):990-1006. view on PubMed
Wang J, Rajbhandari P, Damianov A, Han A, Sallam T, Waki H, Villanueva CJ, Lee SD, Nielsen R, Mandrup S, Reue K, Young SG, Whitelegge J, Saez E, Black DL, Tontonoz P. RNA-binding protein PSPC1 promotes the differentiation-dependent nuclear export of adipocyte RNAs. J Clin Invest. 2017 Mar 01; 127(3):987-1004. view on PubMed
Vuong JK, Lin CH, Zhang M, Chen L, Black DL, Zheng S. PTBP1 and PTBP2 Serve Both Specific and Redundant Functions in Neuronal Pre-mRNA Splicing. Cell Rep. 2016 12 06; 17(10):2766-2775. view on PubMed
Wongpalee SP, Vashisht A, Sharma S, Chui D, Wohlschlegel JA, Black DL. Large-scale remodeling of a repressed exon ribonucleoprotein to an exon definition complex active for splicing. Elife. 2016 11 24; 5. view on PubMed
Zhang X, Chen MH, Wu X, Kodani A, Fan J, Doan R, Ozawa M, Ma J, Yoshida N, Reiter JF, Black DL, Kharchenko PV, Sharp PA, Walsh CA. Cell-Type-Specific Alternative Splicing Governs Cell Fate in the Developing Cerebral Cortex. Cell. 2016 Aug 25; 166(5):1147-1162.e15. view on PubMed
Keppetipola NM, Yeom KH, Hernandez AL, Bui T, Sharma S, Black DL. Multiple determinants of splicing repression activity in the polypyrimidine tract binding proteins, PTBP1 and PTBP2. RNA. 2016 08; 22(8):1172-80. view on PubMed
Vuong CK, Black DL, Zheng S. The neurogenetics of alternative splicing. Nat Rev Neurosci. 2016 May; 17(5):265-81. view on PubMed
Damianov A, Ying Y, Lin CH, Lee JA, Tran D, Vashisht AA, Bahrami-Samani E, Xing Y, Martin KC, Wohlschlegel JA, Black DL. Rbfox Proteins Regulate Splicing as Part of a Large Multiprotein Complex LASR. Cell. 2016 Apr 21; 165(3):606-19. view on PubMed
Linares AJ, Lin CH, Damianov A, Adams KL, Novitch BG, Black DL. The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation. Elife. 2015 Dec 24; 4:e09268. view on PubMed
Lee JA, Damianov A, Lin CH, Fontes M, Parikshak NN, Anderson ES, Geschwind DH, Black DL, Martin KC. Cytoplasmic Rbfox1 Regulates the Expression of Synaptic and Autism-Related Genes. Neuron. 2016 Jan 06; 89(1):113-28. view on PubMed
Black D. Reflections on the RNA journal at 20 and its role in the question of splice site choice. RNA. 2015 Apr; 21(4):497-9. view on PubMed
Sharma S, Wongpalee SP, Vashisht A, Wohlschlegel JA, Black DL. Stem-loop 4 of U1 snRNA is essential for splicing and interacts with the U2 snRNP-specific SF3A1 protein during spliceosome assembly. Genes Dev. 2014 Nov 15; 28(22):2518-31. view on PubMed
Han A, Stoilov P, Linares AJ, Zhou Y, Fu XD, Black DL. De novo prediction of PTBP1 binding and splicing targets reveals unexpected features of its RNA recognition and function. PLoS Comput Biol. 2014 Jan; 10(1):e1003442. view on PubMed
Li Q, Zheng S, Han A, Lin CH, Stoilov P, Fu XD, Black DL. The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation. Elife. 2014; 3:e01201. view on PubMed
Lovci MT, Ghanem D, Marr H, Arnold J, Gee S, Parra M, Liang TY, Stark TJ, Gehman LT, Hoon S, Massirer KB, Pratt GA, Black DL, Gray JW, Conboy JG, Yeo GW. Rbfox proteins regulate alternative mRNA splicing through evolutionarily conserved RNA bridges. Nat Struct Mol Biol. 2013 Dec; 20(12):1434-42. view on PubMed
Babic I, Anderson ES, Tanaka K, Guo D, Masui K, Li B, Zhu S, Gu Y, Villa GR, Akhavan D, Nathanson D, Gini B, Mareninov S, Li R, Camacho CE, Kurdistani SK, Eskin A, Nelson SF, Yong WH, Cavenee WK, Cloughesy TF, Christofk HR, Black DL, Mischel PS. EGFR mutation-induced alternative splicing of Max contributes to growth of glycolytic tumors in brain cancer. Cell Metab. 2013 Jun 04; 17(6):1000-1008. view on PubMed
Zheng S, Black DL. Alternative pre-mRNA splicing in neurons: growing up and extending its reach. Trends Genet. 2013 Aug; 29(8):442-8. view on PubMed
Zheng S, Damoiseaux R, Chen L, Black DL. A broadly applicable high-throughput screening strategy identifies new regulators of Dlg4 (Psd-95) alternative splicing. Genome Res. 2013 Jun; 23(6):998-1007. view on PubMed
Pandya-Jones A, Bhatt DM, Lin CH, Tong AJ, Smale ST, Black DL. Splicing kinetics and transcript release from the chromatin compartment limit the rate of Lipid A-induced gene expression. RNA. 2013 Jun; 19(6):811-27. view on PubMed
Bhatt DM, Pandya-Jones A, Tong AJ, Barozzi I, Lissner MM, Natoli G, Black DL, Smale ST. Transcript dynamics of proinflammatory genes revealed by sequence analysis of subcellular RNA fractions. Cell. 2012 Jul 20; 150(2):279-90. view on PubMed
Keppetipola N, Sharma S, Li Q, Black DL. Neuronal regulation of pre-mRNA splicing by polypyrimidine tract binding proteins, PTBP1 and PTBP2. Crit Rev Biochem Mol Biol. 2012 Jul-Aug; 47(4):360-78. view on PubMed
Anderson ES, Lin CH, Xiao X, Stoilov P, Burge CB, Black DL. The cardiotonic steroid digitoxin regulates alternative splicing through depletion of the splicing factors SRSF3 and TRA2B. RNA. 2012 May; 18(5):1041-9. view on PubMed
Gehman LT, Meera P, Stoilov P, Shiue L, O'Brien JE, Meisler MH, Ares M, Otis TS, Black DL. The splicing regulator Rbfox2 is required for both cerebellar development and mature motor function. Genes Dev. 2012 Mar 01; 26(5):445-60. view on PubMed
Zheng S, Gray EE, Chawla G, Porse BT, O'Dell TJ, Black DL. PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2. Nat Neurosci. 2012 Jan 15; 15(3):381-8, S1. view on PubMed
Gehman LT, Stoilov P, Maguire J, Damianov A, Lin CH, Shiue L, Ares M, Mody I, Black DL. The splicing regulator Rbfox1 (A2BP1) controls neuronal excitation in the mammalian brain. Nat Genet. 2011 May 29; 43(7):706-11. view on PubMed
Sharma S, Maris C, Allain FH, Black DL. U1 snRNA directly interacts with polypyrimidine tract-binding protein during splicing repression. Mol Cell. 2011 Mar 04; 41(5):579-88. view on PubMed
Tang ZZ, Sharma S, Zheng S, Chawla G, Nikolic J, Black DL. Regulation of the mutually exclusive exons 8a and 8 in the CaV1.2 calcium channel transcript by polypyrimidine tract-binding protein. J Biol Chem. 2011 Mar 25; 286(12):10007-16. view on PubMed
Black DL, Gorospe M. Tapas and RNA in Renaissance Spain. RNA Biol. 2010 Mar-Apr; 7(2):130-2. view on PubMed
Damianov A, Black DL. Autoregulation of Fox protein expression to produce dominant negative splicing factors. RNA. 2010 Feb; 16(2):405-16. view on PubMed
Xue Y, Zhou Y, Wu T, Zhu T, Ji X, Kwon YS, Zhang C, Yeo G, Black DL, Sun H, Fu XD, Zhang Y. Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping. Mol Cell. 2009 Dec 25; 36(6):996-1006. view on PubMed
Lee JA, Tang ZZ, Black DL. An inducible change in Fox-1/A2BP1 splicing modulates the alternative splicing of downstream neuronal target exons. Genes Dev. 2009 Oct 01; 23(19):2284-93. view on PubMed
Babic I, Sharma S, Black DL. A role for polypyrimidine tract binding protein in the establishment of focal adhesions. Mol Cell Biol. 2009 Oct; 29(20):5564-77. view on PubMed
Pandya-Jones A, Black DL. Co-transcriptional splicing of constitutive and alternative exons. RNA. 2009 Oct; 15(10):1896-908. view on PubMed
Tang ZZ, Zheng S, Nikolic J, Black DL. Developmental control of CaV1.2 L-type calcium channel splicing by Fox proteins. Mol Cell Biol. 2009 Sep; 29(17):4757-65. view on PubMed
Chawla G, Lin CH, Han A, Shiue L, Ares M, Black DL. Sam68 regulates a set of alternatively spliced exons during neurogenesis. Mol Cell Biol. 2009 Jan; 29(1):201-13. view on PubMed
Stoilov P, Lin CH, Damoiseaux R, Nikolic J, Black DL. A high-throughput screening strategy identifies cardiotonic steroids as alternative splicing modulators. Proc Natl Acad Sci U S A. 2008 Aug 12; 105(32):11218-23. view on PubMed
Xing Y, Stoilov P, Kapur K, Han A, Jiang H, Shen S, Black DL, Wong WH. MADS: a new and improved method for analysis of differential alternative splicing by exon-tiling microarrays. RNA. 2008 Aug; 14(8):1470-9. view on PubMed
Black DL, Zipursky SL. To cross or not to cross: alternatively spliced forms of the Robo3 receptor regulate discrete steps in axonal midline crossing. Neuron. 2008 May 08; 58(3):297-8. view on PubMed
Sharma S, Kohlstaedt LA, Damianov A, Rio DC, Black DL. Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome. Nat Struct Mol Biol. 2008 Feb; 15(2):183-91. view on PubMed
Li Q, Lee JA, Black DL. Neuronal regulation of alternative pre-mRNA splicing. Nat Rev Neurosci. 2007 Nov; 8(11):819-31. view on PubMed
Boutz PL, Stoilov P, Li Q, Lin CH, Chawla G, Ostrow K, Shiue L, Ares M, Black DL. A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev. 2007 Jul 01; 21(13):1636-52. view on PubMed
Lee JA, Xing Y, Nguyen D, Xie J, Lee CJ, Black DL. Depolarization and CaM kinase IV modulate NMDA receptor splicing through two essential RNA elements. PLoS Biol. 2007 Feb; 5(2):e40. view on PubMed
Boutz PL, Chawla G, Stoilov P, Black DL. MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development. Genes Dev. 2007 Jan 01; 21(1):71-84. view on PubMed
Sharma S, Black DL. Maps, codes, and sequence elements: can we predict the protein output from an alternatively spliced locus? Neuron. 2006 Nov 22; 52(4):574-6. view on PubMed
Black DL, Graveley BR. Splicing bioinformatics to biology. Genome Biol. 2006; 7(5):317. view on PubMed
Auweter SD, Fasan R, Reymond L, Underwood JG, Black DL, Pitsch S, Allain FH. Molecular basis of RNA recognition by the human alternative splicing factor Fox-1. EMBO J. 2006 Jan 11; 25(1):163-73. view on PubMed
Xie J, Jan C, Stoilov P, Park J, Black DL. A consensus CaMK IV-responsive RNA sequence mediates regulation of alternative exons in neurons. RNA. 2005 Dec; 11(12):1825-34. view on PubMed
Underwood JG, Boutz PL, Dougherty JD, Stoilov P, Black DL. Homologues of the Caenorhabditis elegans Fox-1 protein are neuronal splicing regulators in mammals. Mol Cell Biol. 2005 Nov; 25(22):10005-16. view on PubMed
Oberstrass FC, Auweter SD, Erat M, Hargous Y, Henning A, Wenter P, Reymond L, Amir-Ahmady B, Pitsch S, Black DL, Allain FH. Structure of PTB bound to RNA: specific binding and implications for splicing regulation. Science. 2005 Sep 23; 309(5743):2054-7. view on PubMed
Sharma S, Falick AM, Black DL. Polypyrimidine tract binding protein blocks the 5' splice site-dependent assembly of U2AF and the prespliceosomal E complex. Mol Cell. 2005 Aug 19; 19(4):485-96. view on PubMed
Amir-Ahmady B, Boutz PL, Markovtsov V, Phillips ML, Black DL. Exon repression by polypyrimidine tract binding protein. RNA. 2005 May; 11(5):699-716. view on PubMed
Black DL. A simple answer for a splicing conundrum. Proc Natl Acad Sci U S A. 2005 Apr 05; 102(14):4927-8. view on PubMed
Hall MP, Huang S, Black DL. Differentiation-induced colocalization of the KH-type splicing regulatory protein with polypyrimidine tract binding protein and the c-src pre-mRNA. Mol Biol Cell. 2004 Feb; 15(2):774-86. view on PubMed
Xie J, Lee JA, Kress TL, Mowry KL, Black DL. Protein kinase A phosphorylation modulates transport of the polypyrimidine tract-binding protein. Proc Natl Acad Sci U S A. 2003 Jul 22; 100(15):8776-81. view on PubMed
Rooke N, Markovtsov V, Cagavi E, Black DL. Roles for SR proteins and hnRNP A1 in the regulation of c-src exon N1. Mol Cell Biol. 2003 Mar; 23(6):1874-84. view on PubMed
Black DL. Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem. 2003; 72:291-336. view on PubMed
