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The interplay between single-stranded binding proteins on RNA secondary structure

Lin, Yi-Hsuan
http://rave.ohiolink.edu/etdc/view?acc_num=osu1429098303

Abstract Details

2015, Doctor of Philosophy, Ohio State University, Physics.
Interactions between RNAs and RNA-binding proteins (RBPs) are significant in post-transcriptional regulation. In this process, an mRNA molecule is bound by many proteins and/or microRNAs to modulate its function. It is therefore an interesting question how these multiple RBPs collaborate to enable combinatorial gene regulation. Here, we propose a possible mechanism which can support this RBP-RBP collaboration, termed "cooperativity". Such a cooperativity can exist merely based on fundamental principles of statistical physics and thermodynamics of RNA structure folding, without considering any further details of RNA and RBP properties. The theory is based on the idea that a successfully binding RBP will prohibit the formation of some originally allowed RNA structures, thus changing the statistical properties of the RNA structure ensemble, as well as the binding probabilities of other RBPs on the same RNA. In addition, this mechanism does not require direct physical interactions between RBPs, and thus supports the long-range characteristic of the cooperativity. Focusing on an RNA with two binding sites, we first calculate the correlation function between the RBPs on the RNA-RBP complex, verifying that this cooperativity exists. We then derive a characteristic difference of free energy differences, i.e. delta delta G, as a quantitative measure of this structure-mediated cooperativity. We apply this measure to a large number of human mRNAs, and discover that this cooperativity is a generic feature. Interestingly, this cooperativity not only affects binding sites in close proximity along the sequence but also configurations in which one binding site is located in the 5’UTR and the other is located in the 3’UTR of the mRNA. Some intriguing interplays between RBPs, microRNA binding sites, and UTR sequences are also disclosed. In the last chapter, we extend our model to handle multiple sequence-specified protein binding sites. We apply this extended model to the binding reaction between the protein HuR and several RNA sequences, theoretically calculating their dissociation constants and comparing with experimental results. We discover that RNA secondary structures are crucial in the interplay between HuR and RNA sequences, verifying the importance of the structure-mediated cooperativity in realistic RNA-protein binding reactions.
Ralf Bundschuh (Advisor)
Eric Braaten (Committee Member)
Mohit Randeria (Committee Member)
Michael Poirier (Committee Member)
132 p.
Biophysics; Molecular Biology; Theoretical Physics
RNA; RNA secondary structure; RNA-protein binding; cooperativity; untranslated region

Recommended Citations

Citations

  • Lin, Y.-H. (2015). The interplay between single-stranded binding proteins on RNA secondary structure [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429098303

    APA Style (7th edition)

  • Lin, Yi-Hsuan. The interplay between single-stranded binding proteins on RNA secondary structure. 2015. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1429098303.

    MLA Style (8th edition)

  • Lin, Yi-Hsuan. "The interplay between single-stranded binding proteins on RNA secondary structure." Doctoral dissertation, Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429098303

    Chicago Manual of Style (17th edition)

osu1429098303
540
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This open access ETD is published by The Ohio State University and OhioLINK.