Abstract

One of the most critical activities of the ribosome is maintenance of the translational reading frame. Although recent structures have revealed numerous interactions between the ribosome and its primary substrates, tRNA and mRNA, how these interactions contribute to reading frame maintenance remains unclear. Understanding this ribosomal activity will directly impact research on programmed ribosomal frameshifting, a class of genetic regulatory mechanisms employed by numerous organisms and viruses, including medically relevant retroviruses and coronaviruses. This proposal has three specific aims: (1) Identify interactions between ribosomal RNA (rRNA) and tRNA important for accurately coupled movement of tRNA and mRNA during translocation. (2) Identify determinants of translocation catalyzed by elongation factor G and by the antibiotic sparsomycin. (3) Use mutant tRNA molecules with expanded anticodons to investigate the contribution of codon-anticodon interactions to reading frame recognition and maintenance. These studies will provide novel insights into the molecular mechanism of reading frame maintenance by the ribosome, a fundamental aspect of gene regulation. Furthermore, this research may significantly contribute to the design of drugs that target HIV.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM072528-03
Application #
7204146
Study Section
Biochemistry Study Section (BIO)
Program Officer
Rhoades, Marcus M
Project Start
2005-04-01
Project End
2010-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$283,507
Indirect Cost

  Institution

Name
Ohio State University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210

  Publications

Vo, My-Nuong; Terrey, Markus; Lee, Jeong Woong et al. (2018) ANKRD16 prevents neuron loss caused by an editing-defective tRNA synthetase. Nature 557:510-515
Dai, Xiongfeng; Zhu, Manlu; Warren, Mya et al. (2018) Slowdown of Translational Elongation in Escherichia coli under Hyperosmotic Stress. MBio 9:
Gibbs, Michelle R; Fredrick, Kurt (2018) Roles of elusive translational GTPases come to light and inform on the process of ribosome biogenesis in bacteria. Mol Microbiol 107:445-454
Ying, Lanqing; Zhu, Hongkun; Shoji, Shinichiro et al. (2018) Roles of specific aminoglycoside-ribosome interactions in the inhibition of translation. RNA :
Hoffer, Eric D; Maehigashi, Tatsuya; Fredrick, Kurt et al. (2018) Ribosomal ambiguity (ram) mutations promote the open (off) to closed (on) transition and thereby increase miscoding. Nucleic Acids Res :
Chen, Menglin; Fredrick, Kurt (2018) Measures of single- versus multiple-round translation argue against a mechanism to ensure coupling of transcription and translation. Proc Natl Acad Sci U S A 115:10774-10779
Gibbs, Michelle R; Moon, Kyung-Mee; Chen, Menglin et al. (2017) Conserved GTPase LepA (Elongation Factor 4) functions in biogenesis of the 30S subunit of the 70S ribosome. Proc Natl Acad Sci U S A 114:980-985
Fleming, Ian M C; Paris, Zden?k; Gaston, Kirk W et al. (2016) A tRNA methyltransferase paralog is important for ribosome stability and cell division in Trypanosoma brucei. Sci Rep 6:21438
Dai, Xiongfeng; Zhu, Manlu; Warren, Mya et al. (2016) Reduction of translating ribosomes enables Escherichia coli to maintain elongation rates during slow growth. Nat Microbiol 2:16231
Liu, Qi; Fredrick, Kurt (2016) Intersubunit Bridges of the Bacterial Ribosome. J Mol Biol 428:2146-64

Showing the most recent 10 out of 39 publications