N6-methyladenosine-dependent rna structural switches modulate RNA-protein interactions /

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Bibliographic Details
Author / Creator:Liu, Nian, author.
Ann Arbor : ProQuest Dissertations & Theses, 2015
Description:1 electronic resource (122 pages)
Format: E-Resource Dissertations
Local Note:School code: 0330
URL for this record:http://pi.lib.uchicago.edu/1001/cat/bib/10773389
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Other authors / contributors:University of Chicago. degree granting institution.
Notes:Advisors: Tao Pan Committee members: Chuan He; Joseph Piccirill.
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Dissertation Abstracts International, Volume: 77-05(E), Section: B.
Summary:Various chemical modifications have been found in cellular RNAs, but their functions remain an uncharted territory. N6 -methyladenosine (m6A), the most abundant and dynamic internal modification in eukaryotic messenger RNA (mRNAs), is indispensable for cell viability, pluripotency and human health, but how m6A achieves such wide-ranging biological functions remains unclear. The m 6A functional studies have been hindered by the lack of methods for its precise detection. To address this problem, I developed one method to detect m6A modification status at nucleotide-resolution, and identified exact m6A sites in human mRNAs and long non-coding RNAs (lncRNAs). Afterwards, I discovered that m6A alters the local RNA structure to control the RNA-structure-dependent accessibility of RNA binding sites, thus affecting RNA-protein interactions; I termed this mechanism 'm6A-switch'. Two members of heterogeneous nuclear ribonucleoproteins (HNRNPs), HNRNPC and HNRNPG, are found to be regulated by m6A-switches. These m6A-switch-regulated HNRNPC/G binding activities affect the RNA abundance and alternative splicing events. These findings illustrate how RNA-binding proteins gain regulated access to their RNA binding sites through m6A-dependent RNA structural remodeling, and provides a new direction for investigating RNA-modification-coded cellular biology.