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Genome-wide Investigation of Cellular Functions for tRNA Nucleus-Cytoplasm Trafficking in the Yeast Saccharomyces cerevisiae

Chu, Hui-Yi
http://rave.ohiolink.edu/etdc/view?acc_num=osu1343397048

Abstract Details

2012, Doctor of Philosophy, Ohio State University, Molecular, Cellular and Developmental Biology.
In eukaryotic cells tRNAs are transcribed in the nucleus and exported to the cytoplasm for their essential role in protein synthesis. This export event was thought to be unidirectional. Surprisingly, several lines of evidence showed that mature cytoplasmic tRNAs shuttle between nucleus and cytoplasm and their distribution is nutrient-dependent. This newly discovered tRNA retrograde process is conserved from yeast to vertebrates. Although how exactly the tRNA nuclear-cytoplasmic trafficking is regulated is still under investigation, previous studies identified several transporters involved in tRNA subcellular dynamics. At least three members of the β-importin family function in tRNA nuclear-cytoplasmic intracellular movement: (1) Los1 functions in both the tRNA primary export and re-export processes; (2) Mtr10, directly or indirectly, is responsible for the constitutive retrograde import of cytoplasmic tRNA to the nucleus; (3) Msn5 functions solely in the re-export process. In this thesis I focus on the physiological role(s) of the tRNA nuclear retrograde pathway. One possibility is that nuclear accumulation of cytoplasmic tRNA serves to modulate translation of particular transcripts. To test this hypothesis, I compared expression profiles from non-translating mRNAs and polyribosome-bound translating mRNAs collected from msn5¿¿¿¿¿¿¿ and mtr10¿¿¿¿¿¿¿ mutants and wild-type cells, in fed or acute amino acid starvation conditions. Microarray data revealed that several amino acid biosynthetic pathways, including the sulfur assimilation, arginine biosynthesis, and leucine biosynthesis pathways, are primary targets of the tRNA trafficking processes. I confirmed the microarray data by both Northern and Western blot analyses. Levels of all tested target proteins involved in such amino acid biogenesis pathways are down-regulated when the tRNA nuclear import or re-export is disrupted. The steady state levels of target total RNAs are similar between wild-type cells and tRNA trafficking defective mutants. The data suggest that the reduction of target proteins most likely results from translation defects of the target mRNAs. This study provides information that tRNA nuclear-cytoplasmic dynamics is connected to amino acid biosynthesis via control at the level of translation.
Anita K. Hopper (Advisor)
Stephen Osmani (Committee Member)
Kurt Fredrick (Committee Member)
Jane Jackman (Committee Member)
Cellular Biology; Genetics; Molecular Biology
tRNA; export; import; Los1; Msn5; Mtr10; translation; polysome; microarray; sulfur; arginine; leucine

Recommended Citations

Citations

  • Chu, H.-Y. (2012). Genome-wide Investigation of Cellular Functions for tRNA Nucleus-Cytoplasm Trafficking in the Yeast Saccharomyces cerevisiae [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1343397048

    APA Style (7th edition)

  • Chu, Hui-Yi. Genome-wide Investigation of Cellular Functions for tRNA Nucleus-Cytoplasm Trafficking in the Yeast Saccharomyces cerevisiae. 2012. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1343397048.

    MLA Style (8th edition)

  • Chu, Hui-Yi. "Genome-wide Investigation of Cellular Functions for tRNA Nucleus-Cytoplasm Trafficking in the Yeast Saccharomyces cerevisiae." Doctoral dissertation, Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1343397048

    Chicago Manual of Style (17th edition)

osu1343397048
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© 2012, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.