David Engelke, Ph.D.

Professor, Biological Chemistry

B.S., University of Wisconsin
Ph.D., Washington University
Postdoctoral, University of California, San Diego

Research Profile

My laboratory investigates several aspects of eukaryotic gene expression, using yeast and human model systems. A combination of biochemistry, molecular genetics, and high resolution microscopy is used to study the forces that both activate and silence nuclear transcription units. We recently found that tRNA genes antagonize transcription of other nearby promoters, and that this phenomenon is related to the three dimensional organization of the activated transcription units. This phenomenon is under study as a potentially widespread negative regulatory mechanism.

In addition to transcription mechanisms, the lab studies structures and functions of RNA enzymes, especially the ubiquitous endoribonuclease RNase P. The highly ordered tertiary structures of the RNA enzymes recognize and cleave pre-tRNA and other substrates through shape recognition, and the nuclear form of RNase P has developed an elaborate subunit structure to allow discrimination of its role in the complex nuclear RNA processing pathways. We are studying how this complex holoenzyme structure recognizes both substrates and elements of the nuclear architecture.

In related projects, we are exploring the ability of nucleic acid chains to recognize a variety of molecular targets, and to apply this knowledge to practical problems. It has become possible to select RNA (or modified RNA) molecules that bind tightly to nearly any molecular surface, starting from a "library" of more than a quadrillion sequences. This allows the production of affinity tags, diagnostics, and potentially potent inhibitors to a wide variety of targets that are not necessarily amenable to antibody production.

Awards

1980-1982 National Research Service Award in Genetics
1993-1994 Faculty Recognition Award, University of Michigan
1999-2000 Board of Directors, the RNA Society
2003 Distinguished Faculty Achievement Award, University of Michigan
2004 Distinguished Faculty Lectureship, University of Michigan Medical School
2005-2009 Senior Fellow, Michigan Society of Fellows
2007 Rackham Graduate School Distinguished Faculty Mentor Award
2008 AAAS Fellow

PubMed Search Term : engelke dr

Publications

Thompson, M, Haeusler, RA, Good, PD, and Engelke, DR. Nucleolar clustering of dispersed tRNA genes. Science 302: 139-1401, 2003
http://www.sciencemag.org/cgi/content/full/302/5649/1399

Paul, CP, Good, PD, Li, SXL, Kleihauer, A, Rossi, JJ, and Engelke, DR. Localized expression of small RNA inhibitors in human cells. Mol. Therapy 7:
237-247. 2003

Coughlin, DJ and Engelke, DR. RNA interference. in RNA Interference: Nuts & Bolts, (D. Engelke, ed.) DNA Press (Eagleville, PA),pp. 13-20, 2003

Scott, FH and Engelke, DR. Identification and characterization of RNA-binding proteins through three-hybrid analysis. in press in “Handbook of RNA Biochemistry” (A.Bindereif, R. Hartmann, A. Schon, E. Westhof, eds.), Wiley-VHF, Weinheim, Germany (2004)

Haeusler, RA and Engelke, DR. (2004) Gene organization in three dimensions: Thinking outside the line. Cell Cycle 3: 273-275 (2004)

Engelke, DR and Rossi, JJ (eds.) Methods in Enzymology, 392 (2005)

Engelke, DR and Hopper, AK. Modified view of tRNA: stability amid sequence diversity. Mol. Cell 21: 144-145. (preview) 2006

Leontis, NB, Altman, R, Berman, HM, Brenner, SE, Brown, J, Engelke, D, Harvey, SC, Holbrook, SR, Jossinet, F, Lewis, SE, Major, F, Mathews, DH, Richardson, J, Williamson, JR, and Westhof, E. The RNA Ontology Consortium: An open invitation to the RNA community. RNA 12: 533-541 2006

Walker, SC and Engelke, DR. Ribonuclease P: The evolution of an ancient RNA enzyme.  Crit. Rev. Biochem. Mol. Biol. 41: 77-102. 2006

Xiao, S, Hsieh, J, Nugent, RL, Coughlin, DJ, Fierke, CA, and Engelke, DR. Functional characterization of the conserved amino acids in Pop1p, the largest common protein subunit of yeast RNases P and MRP. RNA, 12: 1023-1037 2006

Pratt-Hyatt, MJ, Kapadia KM, Wilson TE, and Engelke DR. Increased recombination between active tRNA genes. DNA and Cell Biol. 25: 359-364. 2006

Haeusler, RA and Engelke, DR. Spatial organization of transcription by RNA polymerase III. Nucl. Acids Res. 34: 4826-4836 (2006)

Moir, RD, Lee, JH, Haeusler, RA, Desai, N, Engelke, DR, and Willis, IM. Protein kinase A regulates RNA polymerase III transcription through the nuclear localization of Maf1. Proc. Natl. Acad. Sci. USA 103: 15044-15049 (2006)

Haeusler, RA and Engelke, DR. Spatial organization by RNA polymerase III. Nucl. Acids Res. 34: 4826-4836, 2006

Xiao, S, Hsieh, J, Nugent, RL, Coughlin, DJ, Fierke, CA, and Engelke, DR. Functional characterization of the conserved amino acids in Pop1p, the largest common protein subunit of yeast RNases P and MRP. RNA, 12:1023-1037. 2006

Aspinall, TV, Gordon, JMB, Bennett, HJ, Karahalios, P, Bukowski, J-P, Walker, SC, Engelke, DR, and Avis, JM. Interactions between subunits of Saccharomyces cerevisiae RNase MRP support a conserved eukaryotic RNaseP/MRP architecture. Nucl. Acids Res. 35: 6439-6450. 2007

Haeusler, RA, Pratt-Hyatt, M, Good, PD, and Engelke, DR. Clustering of yeast tRNA genes is mediated by specific association of condensin with tRNA gene transcription complexes. Genes & Devel. 22: 2204-2214, 2008http://genesdev.cshlp.org/content/22/16/2204

Coughlin, DJ, Pleiss, JA, Walker, SC, Guthrie, C, and Engelke, DR. Genome-wide search for RNase P substrates reveals nuclear RNase P is involved in maturation of intron-encoded box C/D small nucleolar RNAs. Proc. Natl. Acad. Sci. USA, 105: 12218-12223, 2008http://www.pnas.org/content/105/34/12218

Walker, SC, Houser-Scott, F, Srisawat, C. and Engelke, DR.  RNA Affinity tags for the rapid purification and investigation of RNAs and RNA-protein complexes. Methods Mol Biol. (488) 23-40, 2008http://www.springerlink.com/content/m62r26481l027238/

Walker, SC and Engelke, DR. A protein-only RNase P in human mitochondria. Cell 135: 412-414 2008 http://www.cell.com/retrieve/pii/S0092867408013007

*Hsieh, J, *Walker, SC, Fierke, CA, and Engelke, DR. Pre-tRNA cleavage by the yeast nuclear RNase P holoenzyme is rate-limited by slow product release. RNA, e-pub ahead of print, 2008 [*= authors contributed equally] http://rnajournal.cshlp.org/content/early/2008/12/17/rna.1309409