Uncovering the structure and function of RNAs using computational and experimental approaches

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2022-12
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O'Leary, Collin A
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Moss, Walter N
Macintosh, Gustavo C
Miller, Allen W
Sashital, Dipali G
Shogren-Knaak, Michael A
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Biochem, Biophysics, and Molecular Biology
Abstract
Ribonucleic acids (RNA) are an important macromolecule involved in the biological regulation of cells. From ribosomal RNA, transfer RNA, messenger RNA, noncoding RNA and more, RNAs are adopting secondary and tertiary structures which perform biological functions. The secondary structure of RNA can be highly informative and the last several years have seen a surge in the experimental and computational methods available to study RNA secondary structure. The work presented in this dissertation provides descriptions of the best practices and criteria to consider when computationally folding and modeling RNA secondary structure. Examples are provided where state-of-the-art RNA modelling programs are applied to viral and human transcriptomes and analyzed in silico (i.e. purely computational) and with experimental (RNA structure probing) data incorporation. In all chapters, different applications, validations, and improvements to the ScanFold program are described. ScanFold is a motif discovery tool that focuses on defining the local secondary structure of longer RNAs and highlights significantly stable (i.e. functional) regions of evolutionarily ordered structure. Here, specific transcripts, viral genomes, and transcriptome wide analyses of a human transcriptome are performed by ScanFold and some resulting motifs are functionally validated. Overall, ScanFold is shown to accurately define RNA secondary structure and is able to home in on known and novel functional motifs.
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