This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this proposal is to build research capacity in the state of Kentucky by establishing a research program that is competitive at the RO1 level of federal funding. The project is designed to understand mechanisms of transcription elongation control and their evolution. We propose to characterize a unique mechanism of transcription elongation control originally discovered in the bacteriophage HK022. HK022 is a temperate phage of the lambda family that infects Escherichia coli. Most members of the lambda phage family use phage encoded proteins to promote gene expression by suppressing transcription termination. HK022 has dispensed with the requirement of an antitermination protein but relies on the direct interaction of sites in the nascent RNA transcript with the host RNA polymerase. These sites, called put, are located in each of the two early operons and are comprised of two stem and loops separated by an unpaired base. The structure of the sites i s important for their function. Mutations that disrupt base pairing reduce antitermination and secondary mutations that reestablish base pairing restore terminator read through. Host mutants that prevent antitermination occur exclusively in a highly conserved zinc-finger domain located at the amino terminus of the beta prime subunit of RNA polymerase. These and other results suggest that the beta prime zinc finger recognizes put RNA and that this domain has a general role in transcription termination. By comparing the gene expression profiles of wild type E. coli with cells that carry mutations in the zinc finger, we hope to identify cellular targets of this highly conserved domain. To increase our understanding of RNA-mediated antitermination and the importance of specific RNA structural elements, we will identify and characterize additional examples of antiterminator RNAs.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016481-06
Application #
7381780
Study Section
Special Emphasis Panel (ZRR1-RI-7 (01))
Project Start
2006-05-01
Project End
2007-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
6
Fiscal Year
2006
Total Cost
$122,320
Indirect Cost
Name
University of Louisville
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
Stenslik, M J; Evans, A; Pomerleau, F et al. (2018) Methodology and effects of repeated intranasal delivery of DNSP-11 in awake Rhesus macaques. J Neurosci Methods 303:30-40
Green, Kimberly A; Becker, Yvonne; Fitzsimons, Helen L et al. (2016) An Epichloƫ festucae homologue of MOB3, a component of the STRIPAK complex, is required for the establishment of a mutualistic symbiotic interaction with Lolium perenne. Mol Plant Pathol 17:1480-1492
Rouchka, Eric C; Flight, Robert M; Fasciotto, Brigitte H et al. (2016) Transcriptional profile of immediate response to ionizing radiation exposure. Genom Data 7:82-5
Saikkonen, Kari; Young, Carolyn A; Helander, Marjo et al. (2016) Endophytic Epichloƫ species and their grass hosts: from evolution to applications. Plant Mol Biol 90:665-75
Smith, Michael E; Monroe, J David (2016) Causes and Consequences of Sensory Hair Cell Damage and Recovery in Fishes. Adv Exp Med Biol 877:393-417
Witkowski, Travis A; Grice, Alison N; Stinnett, DeAnna B et al. (2016) UmuDAb: An Error-Prone Polymerase Accessory Homolog Whose N-Terminal Domain Is Required for Repression of DNA Damage Inducible Gene Expression in Acinetobacter baylyi. PLoS One 11:e0152013
Hofmann, Emily; Webster, Jonathan; Do, Thuy et al. (2016) Hydroxylated chalcones with dual properties: Xanthine oxidase inhibitors and radical scavengers. Bioorg Med Chem 24:578-87
Harrison, Benjamin J; Venkat, Gayathri; Lamb, James L et al. (2016) The Adaptor Protein CD2AP Is a Coordinator of Neurotrophin Signaling-Mediated Axon Arbor Plasticity. J Neurosci 36:4259-75
Rau, Kristofer K; Hill, Caitlin E; Harrison, Benjamin J et al. (2016) Cutaneous tissue damage induces long-lasting nociceptive sensitization and regulation of cellular stress- and nerve injury-associated genes in sensory neurons. Exp Neurol 283:413-27
Young, Carolyn A; Schardl, Christopher L; Panaccione, Daniel G et al. (2015) Genetics, genomics and evolution of ergot alkaloid diversity. Toxins (Basel) 7:1273-302

Showing the most recent 10 out of 244 publications