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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Li, Sanshu; Breaker, Ronald R (2017) Identification of 15 candidate structured noncoding RNA motifs in fungi by comparative genomics. BMC Genomics 18:785
Nelson, James W; Atilho, Ruben M; Sherlock, Madeline E et al. (2017) Metabolism of Free Guanidine in Bacteria Is Regulated by a Widespread Riboswitch Class. Mol Cell 65:220-230
Reiss, Caroline W; Strobel, Scott A (2017) Structural basis for ligand binding to the guanidine-II riboswitch. RNA 23:1338-1343
Wang, Jimin; Moore, Peter B (2017) On the interpretation of electron microscopic maps of biological macromolecules. Protein Sci 26:122-129
Wang, Jimin; Askerka, Mikhail; Brudvig, Gary W et al. (2017) Insights into Photosystem II from Isomorphous Difference Fourier Maps of Femtosecond X-ray Diffraction Data and Quantum Mechanics/Molecular Mechanics Structural Models. ACS Energy Lett 2:397-407
Nelson, James W; Breaker, Ronald R (2017) The lost language of the RNA World. Sci Signal 10:
Lomakin, Ivan B; Stolboushkina, Elena A; Vaidya, Anand T et al. (2017) Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1. Cell Rep 20:521-528
Wang, Jimin; Askerka, Mikhail; Brudvig, Gary W et al. (2017) Crystallographic Data Support the Carousel Mechanism of Water Supply to the Oxygen-Evolving Complex of Photosystem II. ACS Energy Lett 2:2299-2306
Greenlee, Etienne B; Stav, Shira; Atilho, Ruben M et al. (2017) Challenges of Ligand Identification for the Second Wave of Orphan Riboswitch Candidates. RNA Biol :0
Arachchilage, Gayan Mirihana; Sherlock, Madeline E; Weinberg, Zasha et al. (2017) SAM-VI RNAs Selectively Bind S-adenosylmethionine and Exhibit Similarities to SAM-III Riboswitches. RNA Biol :0

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