The objective of this Program is to develop a fundamental physical and chemical understanding of the mechanisms by which RNA molecules and their complexes with proteins carry out their biological functions. During the next five years, several different systems that are involved in the processes of protein synthesis by ribosomes, catalysis by RNA enzymes, RNA helicases and ribo-switches will be studied. While the primary technique used will be single crystal X-ray diffraction, these structural studies will be integrated with genetic, biochemical, chemical and computational approaches. A major goal will be to capture these macromolecular machines at each step of the various processes they carry out, enabling the production of movies showing the molecular motions involved in these mechanisms. Of special interest are the motions that occur in the course of protein synthesis as the ribosome proceeds through its elongation cycle, the co-translational passage of secreted proteins through membranes, the remodeling of RNA by a DEAD box helicase, the mechanisms of riboswitches and other RNAs using allosteric mechanisms, the allosteric consequence of aminoacyl-tRNA synthetase recognition of the tRNA anticodon, and the mechanism of catalysis by a group I intron RNA. Also of interest will be the ways in which the structures and properties of RNA molecules can be utilized to carry out various biological functions often analogous to those performed by proteins.

Public Health Relevance

RNA is continuing to emerge as a central and vital player in biological function and some, such as the ribosome, are targets of antibiotics. Understanding the relations between their structures and functions is essential.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Program Projects (P01)
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Special Emphasis Panel (ZRG1-BCMB-K (40))
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Flicker, Paula F
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Yale University
Schools of Medicine
New Haven
United States
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Meehan, Robert E; Torgerson, Chad D; Gaffney, Barbara L et al. (2016) Nuclease-Resistant c-di-AMP Derivatives That Differentially Recognize RNA and Protein Receptors. Biochemistry 55:837-49
Li, Sanshu; Hwang, Xue Ying; Stav, Shira et al. (2016) The yjdF riboswitch candidate regulates gene expression by binding diverse azaaromatic compounds. RNA 22:530-41
Liu, Bin; Zuo, Yuhong; Steitz, Thomas A (2016) Structures of E. coli σS-transcription initiation complexes provide new insights into polymerase mechanism. Proc Natl Acad Sci U S A 113:4051-6
Askerka, Mikhail; Wang, Jimin; Vinyard, David J et al. (2016) S3 State of the O2-Evolving Complex of Photosystem II: Insights from QM/MM, EXAFS, and Femtosecond X-ray Diffraction. Biochemistry 55:981-4
Gagnon, Matthieu G; Lin, Jinzhong; Steitz, Thomas A (2016) Elongation factor 4 remodels the A-site tRNA on the ribosome. Proc Natl Acad Sci U S A 113:4994-9
Ruff, Karen M; Muhammad, Ayesha; McCown, Phillip J et al. (2016) Singlet glycine riboswitches bind ligand as well as tandem riboswitches. RNA 22:1728-1738
Furukawa, Kazuhiro; Ramesh, Arati; Zhou, Zhiyuan et al. (2015) Bacterial riboswitches cooperatively bind Ni(2+) or Co(2+) ions and control expression of heavy metal transporters. Mol Cell 57:1088-98
Roy, Raktim N; Lomakin, Ivan B; Gagnon, Matthieu G et al. (2015) The mechanism of inhibition of protein synthesis by the proline-rich peptide oncocin. Nat Struct Mol Biol 22:466-9
Polikanov, Yury S; Moore, Peter B (2015) Acoustic vibrations contribute to the diffuse scatter produced by ribosome crystals. Acta Crystallogr D Biol Crystallogr 71:2021-31
Weinberg, Zasha; Kim, Peter B; Chen, Tony H et al. (2015) New classes of self-cleaving ribozymes revealed by comparative genomics analysis. Nat Chem Biol 11:606-10

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