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Quantitative studies of RNA editing and nucleosomal DNA-protein interactions

Chen, Cai
http://rave.ohiolink.edu/etdc/view?acc_num=osu1417523347

Abstract Details

2014, Doctor of Philosophy, Ohio State University, Biophysics.
We investigate the use of computational methods to study RNA editing and kinetic modeling of protein-nucleic acids interaction. RNA is an important biomolecule that is deeply involved in almost all aspects of molecular biology. In order to perform such a variety of functions, the primary RNA transcripts need to be extensively processed. One such post-transcriptional event is RNA editing, which alters transcribed RNAs, resulting in RNA products different from the genomically encoded sequence. Altering can occur through the insertion or deletion of nucleotides relative to the original template (indel RNA editing), or via substitution, in which one nucleotide is changed to another. Many types of RNA editing have been observed in different organisms; however, in many instances the mechanisms of RNA editing are not understood at all. The slime mold Physarum polycephalum is a model organism for the study of RNA editing since it has a very high editing rate and editing is highly reliable. However, previous experiments provided very little information about its mechanism. We showed that the combination of two organisms from the Myxomycetes (Physarum polycephalum and Didymium iridis) can provide a better understanding of insertional RNA editing than one organism alone. We find that using the full transcriptome information of Physarum dramatically improves the accuracy of computational editing site prediction in Didymium and we predicte several new edited genes in Didymium. By comparing the sequences of the two organisms in the vicinity of the editing sites, we establish minimal requirements for the location of the information by which these editing sites are recognized. While indel RNA editing is well known in several lower species, there was one single report that such insertional editing might exist but there is no independent confirmation. We thus explore the possibility of insertional and deletional RNA editing in human. We apply different computational tools that are capable of identifying indel differences between RNA reads and the matching reference genome. With careful further analysis and filtering, we conclude that indel RNA editing is unlikely to be widespread in human. Adenosine to inosine (A-to-I) editing is involved in a number of neurological diseases and cancer; however, comprehensive understanding of the connection between RNA editing and cancer is lacking. We thus systematically investigate A-to-I RNA editing in the cancer transcriptome and establish a strong link between RNA editing and cancer. We identify a number of differentially edited editing sites between cancer subtypes and normals. Furthermore, we demonstrate that cancer and normal samples and even cancer subtypes can be distinguished based on genome-wide RNA editing profiles alone. All eukaryotic DNA is wrapped around histone proteins to form nucleosomes, which compact DNA to the size needed to fit in the nucleus. Recent single molecule experiments found that transcription factor dissociation rates from target sites within nucleosomes are enhanced by two to three orders of magnitude relative to naked DNA. Using rate matrices and the eigenvalues of master equations, we explicitly model this process and find that the dimer mechanism can explain the large, experimentally observed increase in dissociation rate.
Ralf Bundschuh (Advisor)
Michael Poirier (Committee Member)
Juan Alfonzo (Committee Member)
William Ray (Committee Member)
179 p.
Biophysics

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Citations

  • Chen, C. (2014). Quantitative studies of RNA editing and nucleosomal DNA-protein interactions [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1417523347

    APA Style (7th edition)

  • Chen, Cai. Quantitative studies of RNA editing and nucleosomal DNA-protein interactions. 2014. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1417523347.

    MLA Style (8th edition)

  • Chen, Cai. "Quantitative studies of RNA editing and nucleosomal DNA-protein interactions." Doctoral dissertation, Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1417523347

    Chicago Manual of Style (17th edition)

osu1417523347
572
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This open access ETD is published by The Ohio State University and OhioLINK.