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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM022778-35
Application #
7817044
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Program Officer
Flicker, Paula F
Project Start
1997-04-01
Project End
2014-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
35
Fiscal Year
2010
Total Cost
$1,489,931
Indirect Cost
Name
Yale University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Reiss, Caroline W; Strobel, Scott A (2017) Structural basis for ligand binding to the guanidine-II riboswitch. RNA 23:1338-1343
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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
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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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