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Faculty Detail    
Name DAVID SCHNEIDER
 
Campus Address KAUL 442 Zip 0024
Phone  (20-5) -781
E-mail  dschneid@uab.edu
Other websites
     

Education
Undergraduate  University of Georgia, Athens    1998  B.S. (Microbiology and Genetics) 
Graduate  University of Wisconsin, Madison    2003  Ph.D. (Microbiology) 
Fellowship  University of California, Irvine    2007  post-doctoral (Biological Chemistry) 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  GL Ctr for Craniofacial, Oral, & Dental Disorders  GL Ctr for Craniofacial, Oral, & Dental Disorders Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
Cellular and Molecular Biology Program 
Genetics, Genomics and Bioinformatics 
Microbiology 

Biographical Sketch 
David was raised in the suburbs of Atlanta, GA. He obtained his B.S. in microbiology and genetics from the University of Georgia in 1998. As an undergraduate he studied molecular biology of bacteriophage. As a graduate student at the University of Wisconsin (1998 - 2003), he moved up the tree of life to study the effect of small molecule regulators on transcription in bacteria. For his postdoctoral studies at the University of California, Irvine (2003 - 2007), he inched further up the tree of life to study the molecular mechanisms by which RNA polymerase I is regulated in eukaryotic cells. His work continues to focus of defining the mechanisms that control ribosome synthesis in eukaryotic cells.

Society Memberships
Organization Name Position Held Org Link
American Society of Biochemistry and Molecular Biology  member   
American Society of Microbiology  member   
Biophysical Society  member   
RNA Society  member   



Research/Clinical Interest
Title
Control of RNA polymerase I transcription
Description

Ribosome biosynthesis is a complex, energetically expensive process that is directly linked to cell growth and proliferation rates in all living cells. Defining the regulatory circuits that control ribosome synthesis is fundamentally important for understanding cell biology. Furthermore, inhibition of ribosome synthesis has emerged as an excellent method for therapeutic control of cell proliferation. Thus, understanding the processes by which cells control ribosome synthesis will benefit our fundamental understanding of eukaryotic biology and will directly inform ongoing efforts aimed at developing novel anti-cancer chemotherapeutic approaches.

The primary interest in the Schneider lab is in characterizing transcription of the ribosomal DNA (rDNA) by RNA polymerase I (Pol I). Transcription of the rDNA is the first, potentially rate-limiting step in ribosome biosynthesis. Thus the enzymatic properties of Pol I and the trans-acting factors that influence its activity directly affect the protein synthetic capacity of cells.

There are many crucial, unanswered questions concerning early steps in eukaryotic ribosome biosynthesis. To answer these questions, the Schneider lab uses a diverse set of experimental approaches and collaborates with many excellent labs on campus and around the world.

Current projects are focused on the following key questions:

1.       What reaction mechanism describes transcription elongation by Pol I?

2.       How do individual subunits of Pol I influence transcription?

3.       Do trans-acting factors or compounds directly influence nucleotide addition kinetics?

4.       By what mechanisms do shared trans-acting factors influence RNA polymerases I and II?

5.       How does sequence context govern transcriptional pausing by Pol I?

6.       What features of the rDNA influence Pol I transcription elongation and its coupling to processing of the nascent rRNA?

7.       How does dysregulation of rRNA synthesis impact tumor cell growth and regulation thereof?

Selected Publications 
Publication PUBMEDID
Zhang Y, Najmi SM, Schneider DA (2017). Transcription Factors that Influence RNA Polymerases I and II: To What Extent Is Mechanism of Action Conserved? BBA – Gene Regulatory Mechanisms Feb;1860(2):246-255  27989933  
Ucuncuoglu S, Schneider DA, Weeks E, Dunlap DD, Finzi L (2017). Multiplexed, tethered particle microscopy for studies of DNA-enzyme dynamics. Methods Enzymol. 582:415-435  28062044  
Ucuncuoglu S, Engel KL, Purohit PK, Dunlap DD, Schneider DA*, Finzi L* (2016). Direct characterization of transcription elongation by RNA polymerase I. PLoS One Jul 25;11(7):e0159527 *co-corresponding  27455049  
Zhang Y, French SL, Beyer AL, Schneider DA (2016). The Transcription Factor THO Promotes Transcription Initiation and Elongation by RNA Polymerase I. Journal of Biological Chemistry 291(7): 3010 - 3018.  26663077 
Engel KL, French SL, Viktorovskaya OV, Beyer AL, Schneider DA (2015). Spt6 is Essential for rRNA Synthesis by RNA Polymerase I. Molecular and Cellular Biology (in press).  25918242 
Viktorovskaya OV and Schneider DA (2015). Functional Divergence of Eukaryotic RNA Polymerases: Unique Properties of RNA Polymerase I Suit its Cellular Role. Gene 556(1):19-26.  25445273 
Appling FD, Schneider DA (2015). Purification of active RNA polymerase I from yeast. Methods in Molecular Biology 1276:281-9.  25665570 
Dobbin ZC, Katre AA, Steg AD, Erickson BK, Shah MM, Alvarez RD, Conner MG, Schneider D, Chen D, Landen CN (2014). Using heterogeneity of the patient-derived xenograft model to identify the chemoresistant population in ovarian cancer. Oncotarget 5(18): 8750-64.  25209969 
Lu L, Zheng L, Luo W, Dujardin G, Kwan T, Potochick NR, Thompson SR, Schneider DA, King PH (2014). Hu Antigen R (HuR) is a Positive Regulator of RNA Binding Proteins TDP-43 and FUS/TLS: Implications for Amyotrophic Lateral Sclerosis. Journal of Biological Chemistry 289: 31792-31804.  25239623 
Mroczek ES, Ippolito GC, Rogosch T, Hoi KH, Hwangpo TA, Brand MG, Zhuang Y, Liu CR, Schneider DA, Zemlin M, Brown EE, Georgiou G,Schroeder HW Jr (2014). Differences in the composition of the human antibody repertoire by B cell subsets in the blood. Frontiers Immunol 5(96): 1-14.  24678310 
Xu Y, Yang H, Joo HY, Yu JH, Smith AD, Schneider D, Chow LT, Renfrow M, Wang H (2013). Ubp-M serine 552 phosphorylation by cyclin-dependent kinase 1 regulates cell cycle progression. Cell Cycle 1;12 (19): 3219-3227.  24013421 
Viktorovskaya OV, Engel KL, French SL, Cui P, Vandeventer PJ, Pavlovic EM, Beyer AL, Kaplan CD, Schneider DA (2013). Divergent contributions of conserved active site residues to transcription by eukaryotic RNA polymerases I and II. Cell Reports 4(5): 974-984.  23994471 
Stepanchick A, Zhi H, Cavanaugh AH, Rothblum K, Schneider DA, Rothblum LI (2013). DNA-binding by the ribosomal DNA transcription factor Rrn3 is essential for ribosomal DNA transcription. Journal of Biological Chemistry 288(13): 9135-9144.  23393135 
Zhang Y, Anderson SJ, French SL, Sikes ML, Viktorovskaya OV, Huband J, Holcomb K, Hartman IV J, Beyer AL, Schneider DA (2013). The SWI/SNF chromatin remodeling complex influences transcription by RNA polymerase I in Saccharomyces cerevisiae. PLoS One 8(2): e56793.  23437238 
Schneider DA (2012). Quantitative analysis of transcription elongation by RNA polymerase I in vitro. Methods in Molecular Biology 809: 579-591.  22113301  
Bedwell GJ, Appling FD, Anderson SJ, Schneider DA (2012). Efficient Transcription by RNA Polymerase I using Recombinant Core Factor. Gene 492: 94-99.  22093875  
Schneider DA (2012). RNA polymerase I activity is regulated at multiple steps in the transcription cycle: recent insights into factors that influence transcription elongation. Gene 493: 176–184.  21893173  
Anderson SJ, Sikes ML, Zhang Y, French SL, Salgia S, Beyer AL, Nomura M, Schneider DA (2011). The transcription elongation factor Spt5 influences transcription by RNA polymerase I positively and negatively. J. Biol. Chem.   21467039 
Viktorovskaya OV, Appling FD, Schneider DA (2011). Yeast transcription elongation factor SPT5 associates with RNA polymerase I and RNA polymerase II directly. J. Biol. Chem.  21467036 
Zhang Y, Smith IV AD, Renfrow MB, Schneider DA (2010) The RNA polymerase-associated factor 1 complex (Paf1C) directly increases the elongation rate of RNA polymerase I and is required for efficient regulation of rRNA synthesis. J. Biol. Chem. 285: 14152-14159. PMC2863250   20299458 
Zhang Y, Sikes ML, Beyer AL, Schneider DA (2009). The Paf1 complex is required for efficient transcription elongation by RNA polymerase I. Proc. Natl. Acad. Sci. USA. 106: 2153-2158. PMC2650124  19164765 
Clemente-Blanco A, Mayán-Santos M, Schneider DA, Machín F, Jarmuz A, Tschochner H, Aragón L (2009). Cdc14 inhibits transcription by RNA polymerase I during anaphase. Nature 458: 219-222.  19158678 
French SL, Osheim YN, Schneider DA, Sikes ML, Fernandez CF, Copela LA, Misra VA, Nomura M, Wolin SL, Beyer AL (2008). Visual analysis of the yeast 5S rRNA gene transcriptome: Regulation and role of La protein. Mol. Cell Biol. 28: 4576-4587.  18474615 
Schneider DA, Michel A, Sikes MJ, Vu L, Dodd J, Salgia SR, Osheim YN, Beyer AL, and Nomura M (2007). Transcription elongation by RNA polymerase I is linked to efficient rRNA processing and ribosome assembly. Mol. Cell. 26: 217-229.  17466624 
Schneider DA, French SL, Osheim YN, Bailey AO, Vu L, Dodd J, Yates JR, Beyer AL, and Nomura M (2006). RNA Polymerase II elongation factors Spt4p and Spt5p play roles in transcription elongation by RNA polymerase I and rRNA processing. Proc. Natl. Acad. Sci. USA. 103: 12707-12712.  16908835 
Tongaonkar P, French S, Oakes M, Vu L, Schneider DA, Beyer A, and Nomura M (2005). Histones are required for transcription of yeast rRNA genes by RNA polymerase I. Proc. Natl. Acad. Sci. USA. 102: 10129-34.  16002464 
Schneider DA and Nomura M (2004). RNA polymerase I remains intact without subunit exchange through multiple rounds of transcription in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA. 101: 15112-15117.  15477604 
Paul BJ, Barker MM, Ross W, Schneider DA, Webb C, Foster JW, and Gourse RL (2004). DksA: A critical component of the transcription initiation machinery that potentiates the regulation of rRNA promoters by ppGpp and the initiating NTP. Cell. 118: 311-322.  15294157 
Schneider DA, Murray HD, and Gourse RL (2003). Measuring control of transcription initiation by changing concentrations of nucleotides and their derivatives. Methods Enzymol. 370: 606-617.  14712679 
Schneider DA and Gourse RL (2004). Relationship between growth rate and ATP concentration in Escherichia coli: A bioassay for available cellular ATP. J. Biol. Chem. 279: 8262-8268.  14670952 
Schneider DA and Gourse RL (2003). Changes in the concentrations of guanosine 5-diphosphate 3-diphosphate and the initiating nucleoside triphosphate account for inhibition of rRNA transcription in fructose 1,6 diphosphate aldolase (fda) mutants. J. Bacteriol. 185(20): 6192-6194.  14526031 
Schneider DA and Gourse RL (2003). Changes in Escherichia coli rRNA promoter activity correlate with changes in initiating nucleoside triphosphate (iNTP) and guanosine 5'-diphosphate 3'-diphosphate (ppGpp) concentrations after induction of feedback control of ribosome synthesis. J. Bacteriol. 185(20): 6185-6191.  14526030 
Murray HD, Schneider DA, Gourse RL (2003). Control of rRNA expression by small molecules is dynamic and nonredundant. Mol. Cell, 12(1):125-34.  12887898 
Ross W, Schneider DA, Paul BJ, Mertens A, Gourse RL (2003). An intersubunit contact stimulating transcription initiation by E. coli RNA polymerase: interaction of the alpha C-terminal domain and sigma region 4. Genes Dev. 17(10):1293-1307.  12756230 
Schneider DA, Ross W, Gourse RL (2003). Control of rRNA expression in Escherichia coli. Curr. Opin. Microbiol. 6(2):151-156.  12732305 
Schneider DA, Gaal T, Gourse RL (2002). NTP-sensing by rRNA promoters in Escherichia coli is Direct. Proc. Natl. Acad. Sci. USA, 99: 8602-8607.  12060720 
Burke J, Schneider D, and Westpheling J (2001). Generalized transduction in Streptomyces. Proc. Natl. Acad. Sci. USA, 98: 6289-6294.   11353836 

Keywords
cancer, gene expression, RNA processing, ribosomes, transcription, drug development, enzymology