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BAEZ_Dissertation_May2018.pdf (5.26 MB)

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RNA Secondary Structures: from Biophysics to Bioinformatics

Baez, William David
http://rave.ohiolink.edu/etdc/view?acc_num=osu1525714439675315

Abstract Details

2018, Doctor of Philosophy, Ohio State University, Physics.
We investigate aspects of RNA secondary structure from the view point of theoretical biophysics and from view point of bioinformatics. From the existence of a novel thermodynamic phase transition to the fundamental mechanisms of life, RNA continues to act as wellspring of new discoveries. RNA forms elaborate secondary structures through intramolecular base pairing. These structures perform critical biological functions within each cell. Due to the availability of a polynomic algorithm to calculate the partition function, they are also a suitable model system for the statistical physics of disordered systems. In this model, below the denaturation temperature random RNA secondary structures can exist in one of two phases: a strongly disordered, low-temperature glass phase and a weakly disordered, high-temperature molten phase. The probability of two bases pairing in these phases has been shown to decay with the distance between the two bases with an exponent 3/2 and 4/3 in the molten and glass phases, respectively. Drawing on previous results from a renormalized field theory of the glass transition, we numerically study this transition and introduce two order parameters that determines the location of the critical point, and explore the driving mechanism behind this transition. Within a cell's genome regulatory elements can often be found within the vicinity of the genes they regulate. In prokaryotes, a common translational regulatory element, the Shine Dalgarno sequence, has been found to be largely absent from entire phyla of bacteria. This sequence element is part of the textbook model of translation initiation. To understand how Shine Dalgarno independent bacteria, such as F. johnsoniae, a member of the phylum Bacteroidetes, initiates translation, we used high-thoughput RNA sequencing and ribosome profiling data to investigate the impact of mRNA secondary structure near a gene's initiation site. We found evidence that strongly implicates the role that unstructured or unstable mRNA structures play in these understudied organisms. Finally, we again use high-throughput RNA sequencing and ribosome profiling data to study the impact of Fhit loss on human cells. Our findings show that Fhit expression impacts the translation of a number of cancer associated genes, and they support the hypothesis that Fhit's genome protective/tumor suppressor function is associated with post-transcriptional changes in expression of genes whose dysregulation contributes to malignancy.
Ralf Bundschuh (Advisor)
131 p.
Bioinformatics; Biophysics
RNA Secondary Structures; theoretical biophysics; bioinformatics

Recommended Citations

Citations

  • Baez, W. D. (2018). RNA Secondary Structures: from Biophysics to Bioinformatics [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1525714439675315

    APA Style (7th edition)

  • Baez, William. RNA Secondary Structures: from Biophysics to Bioinformatics. 2018. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1525714439675315.

    MLA Style (8th edition)

  • Baez, William. "RNA Secondary Structures: from Biophysics to Bioinformatics." Doctoral dissertation, Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1525714439675315

    Chicago Manual of Style (17th edition)

osu1525714439675315
244
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This open access ETD is published by The Ohio State University and OhioLINK.