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- Title
Post -Transcriptional Regulation of Cardiac Sarcomere Protein Titin Through 3' Untranslated Regions.
- Authors
Shrout, Tara; Lim, Chee; Hillyer, Julian
- Abstract
Titin is the largest known protein in the human body, and forms the backbone of all striated muscle sarcomeres. The elastic nature of titin within each sarcomere is an important component of muscle compliance and functionality. Due to its size, a significant amount of energy is expended to synthesize titin. Thus, we postulate that titin gene expression is under strict regulatory control in order to conserve cellular resources. In general, gene expression is mediated in part by post-transcriptional control elements located within the 5' and 3' untranslated regions (UTRs) of mature mRNA. The 3'UTR in particular contains structural features that affect binding capacity to other RNA components, such as MicroRNA, which control mRNA localization, translation, and degradation. The degree and significance of the regulatory effects mediated by two determined variants of titin's 3' UTR were evaluated in Neonatal Rat Ventricular Myocyte and Human Embryonic Kidney cell lines. Recombinant plasmids to transfect these cells lines were engineered by insertion of the variant titin 3'UTR 431- and 1047-base pairs sequences into luciferase reporter vectors. Quantitative changes in luciferase activity due to the recombinants proportionally represented the effect titin's respective 3'UTR conferred on downstream post-transcriptional expression relative to the control. The effect due to titin's shorter 3'UTR sequence was inconclusive; however, results illustrated that titin's longer 3'UTR sequence caused a 35 percent decrease in luciferase activity. Secondary structural analysis of the two sequences revealed differential folding patterns that could affect the stability and degree of MicroRNA-binding within titin's variant 3'UTR sequences. Such potential changes in titin regulation, via 3'UTRs, impose significant implications for cardiovascular care. In order to maintain striated cardiac muscle under varying disease conditions, titin abundance and turnover must adapt. Although evidence of different titin 3'UTR lengths have not yet been linked to certain disease states, theories are postulated in this study, and catalyze further research to better understand how the cardiac sarcomere protein titin is regulated.
- Subjects
HUMAN body; GENE expression; CONNECTIN; MUSCLE proteins; MESSENGER RNA; LABORATORY rats
- Publication
Vanderbilt Undergraduate Research Journal, 2013, Vol 9, p1
- ISSN
1555-788X
- Publication type
Article
- DOI
10.15695/vurj.v9i0.3772