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Endoribonuclease-mediated mRNA decay involves the selective targeting of PMR1 to polysome-bound substrate

Yang, Feng
http://rave.ohiolink.edu/etdc/view?acc_num=osu1111267563

Abstract Details

2005, Doctor of Philosophy, Ohio State University, Ohio State Biochemistry Program.
Endonuclease-mediated mRNA decay is one important pathway of regulating mRNA turnover rate, and PMR1 is the best characterized vertebrate mRNA endonuclease. It was originally identified as an estrogen-induced ribonuclease activity that catalyzed the degradation of Xenopus albumin mRNA. Although the mechanism involved in targeting substrate mRNA to degradation is unknown, previous evidence suggested that the functional unit of endonuclease-mediated mRNA decay is a ~680 kDa polysome-bound complex. In this study, I have demonstrated that endonuclease-mediated mRNA decay catalyzed by PMR1 is distinctly different from the general exonuclease-mediated mRNA decay pathways, and PMR1 selectively targets and degrades its translating substrate mRNA by formation of a ~680 kDa polysome-bound complex that contains both PMR1 and its substrate mRNA. I have identified two domains involved in targeting PMR1 to polysomes, an N-terminal domain that lies between residues 100 and 150, and a C-terminal domain that lies within the last 100 residues. Loss of either domain inactivated PMR1 targeting to polysomes and stabilized albumin mRNA. A phosphorylated tyrosine residue within the C-terminal polysome targeting domain is required for PMR1-mediated mRNA decay. Changing this tyrosine to phenylalanine inactivated the targeting of PMR1 to polysomes, blocked binding of PMR1 to the functional complex containing its substrate mRNA, prevented the targeting of a GFP fusion protein to this complex, and stabilized albumin mRNA to degradation by PMR1 in vivo. These results indicate that endonuclease-mediated mRNA decay occurs on a polysome-bound complex containing PMR1 and its substrate mRNA. Furthermore, the requirement for tyrosine phosphorylation of PMR1 directly links this effector endoribonuclease to key signal transduction pathways.
Daniel Schoenberg (Advisor)
Biology, Molecular
Endoribonuclease; mRNA decay; Polysomal ribonuclease 1; Tyrosine phosphorylation

Recommended Citations

Citations

  • Yang, F. (2005). Endoribonuclease-mediated mRNA decay involves the selective targeting of PMR1 to polysome-bound substrate [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1111267563

    APA Style (7th edition)

  • Yang, Feng. Endoribonuclease-mediated mRNA decay involves the selective targeting of PMR1 to polysome-bound substrate. 2005. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1111267563.

    MLA Style (8th edition)

  • Yang, Feng. "Endoribonuclease-mediated mRNA decay involves the selective targeting of PMR1 to polysome-bound substrate." Doctoral dissertation, Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1111267563

    Chicago Manual of Style (17th edition)

osu1111267563
680
© 2005, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.