This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of this project is to understand a unique mechanism of transcription elongation control originally discovered in the bacteriophage HK022. Most members of the lambda phage family use phage-encoded proteins to promote early gene expression by suppressing transcription termination. HK022 does not encode an antitermination protein but relies instead on the direct interaction of sites in the nascent transcript with RNA polymerase. The specific hypothesis is that the activity of RNA-based antiterminators depends upon the recognition of sequence and structural information in the nascent transcript by RNA polymerase. This hypothesis is based upon previous studies that 1) have shown that mutations that disrupt base pairing in the RNA reduce antitermination and secondary mutations that re-establish base pairing restore terminator read through 2) interchanging segments of antiterminator RNAs drastically affects activity, and 3) RNA-mediated antitermination is blocked by mutations in the beta prime subunit of E. coli RNA polymerase. The goal of this proposal is to identify the required sequence and structural elements of RNA based antiterminators.
The specific aims are: 1) to identify additional examples of antiterminator RNAs in lambdoid phages;2) to use in vivo, in vitro and in silico approaches to determine the structurally and functionally important features of the newly identified antiterminator RNAs;and 3) to complete the annotation of two new phage genomes that possess RNA-based antiterminators. The antiterminator sequences discovered in HK022 provide unique examples of RNAs that control gene expression by directly modifying the transcription apparatus. Unusual modes of gene regulation are potential targets for drug design. Therefore, a better understanding of antiterminator RNAs and their recognition by RNA polymerase may facilitate the discovery or development of therapeutic agents capable of altering the expression of virulence genes and thus attenuating disease processes.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016481-11
Application #
8360107
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
11
Fiscal Year
2011
Total Cost
$63,877
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
Green, Kimberly A; Becker, Yvonne; Fitzsimons, Helen L et al. (2016) An Epichloë 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
Saikkonen, Kari; Young, Carolyn A; Helander, Marjo et al. (2016) Endophytic Epichloë species and their grass hosts: from evolution to applications. Plant Mol Biol 90:665-75
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
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
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
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
Becker, Yvonne; Eaton, Carla J; Brasell, Emma et al. (2015) The Fungal Cell-Wall Integrity MAPK Cascade Is Crucial for Hyphal Network Formation and Maintenance of Restrictive Growth of Epichloë festucae in Symbiosis With Lolium perenne. Mol Plant Microbe Interact 28:69-85
Gemmell, Amber P; Marcus, Jeffrey M (2015) A tale of two haplotype groups: Evaluating the New World Junonia ring species hypothesis using the distribution of divergent COI haplotypes. Syst Entomol 40:532-546

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