The giant myofilament protein titin is indispensable for the structural integrity and function of the sarcomere, however, little is known regarding the turnover of titin within the complex macromolecular sarcomere structure in contracting cardiomyocytes. This dissertation presents novel and unique insight into the homeostatic control of titin in the cardiac sarcomere; nevertheless, the projects described in this dissertation served to elucidate key components in our understanding of the titin life cycle. The experiments described in the following chapters have addressed 3 major findings. 1) Titin is post-transcriptionally regulated at its 5â-UTR via cis-regulatory uORFs. 2) Titin is post-transcriptionally regulated by miR-26a/b at its 3â-UTR. 3) Titin is not a dynamic and mobile protein that is undergoing continuous exchange between myofibrils.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-05222017-140610 |
| Date | 07 June 2017 |
| Creators | Cadar, Adrian Gabriel |
| Contributors | Charles E. Cobb, PhD, Wenbiao Chen, PhD, Anne K. Kenworthy, PhD, Chee C. Lim, PhD, Charles C. Hong, MD/PhD, Owen McGuinness, PhD |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-05222017-140610/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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