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    Connecting Mutations of the RNA Polymerase II C-Terminal Domain to Complex Phenotypic Changes Using Combined Gene Expression and Network Analyses

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    Author
    Rogers, Carlyle; Guo, Zhenhua; Stiller, John W.
    Abstract
    The C-terminal domain (CTD) of the largest subunit in DNA-dependent RNA polymerase II (RNAP II) is essential for mRNA synthesis and processing, through coordination of an astounding array of protein-protein interactions. Not surprisingly, CTD mutations can have complex, pleiotropic impacts on phenotype. For example, insertions of five alanine residues between CTD diheptads in yeast, which alter the CTD's overall tandem structure and physically separate core functional units, dramatically reduce growth rate and result in abnormally large cells that accumulate increased DNA content over time. Patterns by which specific CTD-protein interactions are disrupted by changes in CTD structure, as well as how downstream metabolic pathways are impacted, are difficult to target for direct experimental analyses. In an effort to connect an altered CTD to complex but quantifiable phenotypic changes, we applied network analyses of genes that are differentially expressed in our five alanine CTD mutant, combined with established genetic interactions from the Saccharomyces cerevisiae Genome Database (SGD). We were able to identify candidate genetic pathways, and several key genes, that could explain how this change in CTD structure leads to the specific phenotypic changes observed. These hypothetical networks identify links between CTD-associated proteins and mitotic function, control of cell cycle checkpoint mechanisms, and expression of cell wall and membrane components. Such results can help to direct future genetic and biochemical investigations that tie together the complex impacts of the CTD on global cellular metabolism.
    URI
    http://hdl.handle.net/10342/5458
    Subject
     Gene expression; Chromosomes; Phenotypes; Yeast; Genetic networks 
    Date
    2010
    Citation:
    APA:
    Rogers, Carlyle, & Guo, Zhenhua, & Stiller, John W.. (January 2010). Connecting Mutations of the RNA Polymerase II C-Terminal Domain to Complex Phenotypic Changes Using Combined Gene Expression and Network Analyses. PLoS ONE, (5:6), p.1-8. Retrieved from http://hdl.handle.net/10342/5458

    Display/Hide MLA, Chicago and APA citation formats.

    MLA:
    Rogers, Carlyle, and Guo, Zhenhua, and Stiller, John W.. "Connecting Mutations of the RNA Polymerase II C-Terminal Domain to Complex Phenotypic Changes Using Combined Gene Expression and Network Analyses". PLoS ONE. 5:6. (1-8.), January 2010. April 19, 2021. http://hdl.handle.net/10342/5458.
    Chicago:
    Rogers, Carlyle and Guo, Zhenhua and Stiller, John W., "Connecting Mutations of the RNA Polymerase II C-Terminal Domain to Complex Phenotypic Changes Using Combined Gene Expression and Network Analyses," PLoS ONE 5, no. 6 (January 2010), http://hdl.handle.net/10342/5458 (accessed April 19, 2021).
    AMA:
    Rogers, Carlyle, Guo, Zhenhua, Stiller, John W.. Connecting Mutations of the RNA Polymerase II C-Terminal Domain to Complex Phenotypic Changes Using Combined Gene Expression and Network Analyses. PLoS ONE. January 2010; 5(6) 1-8. http://hdl.handle.net/10342/5458. Accessed April 19, 2021.
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