RNA is amazing. We found that without changing the backbone connectivity, RNA can maintain structural conservation in 3D via topology switches, at a single residue level. I developed a method of representing RNA structure in multiresolution, called the PBR approach (P stands for Phosphate; B stands for Base; R stands for Ribose). In this method, structural data is viewed through a series of resolutions from finest to coarsest. At a single nucleotide resolution (fine resolution), RNA is abstruse and elaborate with structural insertions/deletions, strand clips, and 3,2-switches. The compilation of structural deviations of RNA, called DevLS (Deviations of Local Structure), provides a new descriptive language of RNA structure, allowing one to systematize and investigate RNA structure.
Using PBR analysis, a total of 103 tetraloops within the crystal structures of the 23s rRNA of H. marismortui and the 70s rRNA of T. thermophilus are found and classified. Combining them, I constructed a 'tetraloop family tree', using a tree formalism, to unify and re-define the tetraloop motif and to represent relationships between tetraloops, as grouped by DevLS.
To date, structural alignment of very large RNAs remains challenge due to the large size, intricate backbone choreography, and tertiary interactions. To overcome these obstacles, I developed a concept of structural anchors along with a 'Divide and Conquer' strategy for performing superimposition of 23s rRNAs. The successful alignment and superimpositions of the 23s rRNAs of T. thermophilus and H. marismortui gives an overall RMSD of atomic positions of 1.2 Å, as utilized 73% of RNA backbone atoms (~ 2129 residues).
By using principles of inorganic chemistry along with structural alignment technique as described above, a recurrent magnesium-binding motif in large RNAs is revealed. These magnesium-binding motifs play a critical role in the framework of the ribosomal PTC by their locations, topologies, and coordination geometries. Common features of Mg2+-mc's include direct phosphate chelation of two magnesium ions in the form of Mg2+(i)-(O1P-P-O2P)-Mg2+(j), phosphate groups of adjacent RNA residues as ligands of a given Mg2+, and undulated RNA surfaces with unpaired and unstacked bases.
| Identifer | oai:union.ndltd.org:GATECH/oai:smartech.gatech.edu:1853/26634 |
| Date | 25 August 2008 |
| Creators | Hsiao, Chiaolong |
| Publisher | Georgia Institute of Technology |
| Source Sets | Georgia Tech Electronic Thesis and Dissertation Archive |
| Detected Language | English |
| Type | Dissertation |
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