Browsing by Author "Stu Maxwell, Committee Member"

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • No Thumbnail Available
    Prediction and Modeling of the Structure of 16S rRNA
    (2005-11-29) Fanning, Patricia Babin; Paul Agris, Committee Member; Stu Maxwell, Committee Member; Paul Wollenzien, Committee Chair; James Brown, Committee Member
    The ribosome is a complex macromolecule responsible for the translation of genetic information into proteins. Experimental data has provided clear evidence that the ribosome undergoes conformational changes during the process of translation. The size of the ribosome coupled with its dynamic nature has made it difficult to determine the detailed structure of the ribosome using traditional structural analysis techniques (e.g. NMR or crystallography). Recently, crystal structures of the ribosome of several organisms have been determined. The crystal structures are consistent with ~90% of the data obtained experimentally. The areas of the crystal structure of the ribosome which are inconsistent with experimental data are concentrated primarily in the areas of the ribosome known to be actively involved in the process of translation. The computational techniques utilized in this project provide an alternative method for generating structures that are consistent with all the experimental data. In the first phase of the project, MC-SYM, a constraint satisfaction algorithm, was used to generate detailed three-dimensional models for two regions in the RNA portion of the small subunit of the ribosome known to be actively involved in translation: 921- 930/1387-1396 and 1399-1410/1490-1504. The models generated are consistent with the predicted secondary structure, chemical reactivity data, mutagenesis data and crosslinking data. The second phase of the project used statistical methods to identify the highest probability base triples in the small subunit of the ribosome. The most likely candidates for base triples in the ribosome were identified as base triples involving the single stranded nucleotide 121and the 124:237 or the 125:236 base pair. Isomorphic modeling using the algorithm ISOPAIR indicated that a base triple consisting of an interaction between 121 and the 124:237 was the most likely to produce an isomorphic structure for the most frequently occurring sequences for this region. MC-SYM was used then used to construct a model for the 122-127/234-239 base paired region that included a base triple interaction between the single stranded nucleotide 121 and the 124:237 base pair.
  • No Thumbnail Available
    The RNA World: A Look at Ribonuclease P RNA, Small Nucleolar RNA, 6S RNA, and the Small Ribosomal Subunit
    (2006-11-28) Ellis, Joseph; Stu Maxwell, Committee Member; Bob Kelly, Committee Member; Amy Grunden, Committee Member; James Brown, Committee Chair
    The term RNA world was first coined in 1986 by W. Gilbert. It was largely based on the observation that RNA, not protein, was responsible for the most critical roles in Bacteria, Archaea and Eukaryotes. Although the RNA world means different things to different researchers Gerald Joyce and Leslie Orgel were able to surmise three common characteristic of all RNA World hypotheses: 1) Genetic continuity was dependent on the replication of RNA; 2) Base pairing was predicated on the Watson - Crick Model; 3) Genetically encoded proteins were not catalytic. An example of an ancient catalytic RNA observed in modern cells is ribonuclease P (RNase P). RNase P is responsible for the maturation of pre-tRNA by cleaving the 5' leader to form the mature tRNA and is widely believed to be a relic from the RNA world. Other functionally important RNAs are: small nucleolar RNAs (snoRNAs) which generally catalyze sequence specific 2'-O- ribose methylation and pseudouridylation of ribosomal RNAs, 6S RNAs responsible for the modulation of RNA polymerase, and the small ribosomal subunit which plays a significant role in the synthesis of proteins and peptides. Recent research advances have shown all of these RNAs are important in medical and biotechnology applications. Here we describe our research efforts with these functionally important and essential RNAs: ribonuclease P RNA, small nucleolar RNA, 6S RNA, and the small ribosomal subunit. The cellular processes, database generation, bioinformatics approaches, and the application of RNA in biotechnology are detailed in this work.