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TRANSCRIPTIONAL CONTROL OF AN ESSENTIAL RIBOZYME AND AN EGFR LIGAND REVEAL SIGNIFICANT EVENTS IN INSECT EVOLUTION

Manivannan, Sathiya Narayanan
http://rave.ohiolink.edu/etdc/view?acc_num=osu1437053490

Abstract Details

2015, Doctor of Philosophy, Ohio State University, Molecular, Cellular and Developmental Biology.
In this thesis I examined the regulation of two Drosophila genes: RNase P RNA (RPR), which codes for the ribozyme component of an essential pre-tRNA processing enzyme, and vein (vn), which encodes a secreted ligand for the Epidermal growth factor receptor (Egfr). These two genes represent two different modes of gene regulation—while RPR is ubiquitously expressed, vn has a complex pattern of expression in specific tissues. Further, RPR is present in the intron of the Drosophila ATPsynC gene and transcriptionally co-regulated with the recipient gene. In contrast, vn is an independent gene with a complex promoter. The transcriptional regulation of Drosophila RPR is intriguing because it lacks signals for Pol III transcription and is in the intron of a Pol II transcribed gene. This is in contrast to other eukaryotic RPR genes studied thus far, which are all typical Pol III regulated genes. Using biochemical analyses, I have demonstrated that the annotated gene, the only copy of RPR in the genome, codes for the bona fide Drosophila RPR. My reporter gene study demonstrated that RPR is produced in a splicing independent fashion and its biogenesis is dependent on the Pol II promoter of the recipient gene. Pol II dependent transcription of RPR seems to be a hallmark of two major groups in Arthropods - Hexapods and Vericrustaceans. Current data supports a genetic event that caused the switch from an independent Pol III transcribed RPR to a Pol II dependent RPR that occurred approximately 500 million years ago. After the initial change the Pol II transcribed RPR moved again, as evident in the different in RPR recipient genes in different orders of Hexapoda. The orthologs of RPR recipient genes in D. melanogaster are expressed throughout development in all tissues, suggesting that ubiquitous expression may be one of the characteristics of RPR recipient genes. While the transcriptional coupling leads to the ubiquitous expression of RPR, vn is expressed in a dynamic pattern in the wing imaginal disc. The development of the two cell-layered wing imaginal disc, which gives rise to the adult wing and the body wall, is dependent on Egfr signaling mediated by Vn. I found that Dpp-mediated TGF-Beta signaling from the peripodial cell layer induces the de novo expression of vn in the adjacent disc proper cell layer. This positive paracrine signaling by Dpp is transient and unidirectional. Subsequent to direct paracrine induction by Dpp, the vn expression domain expands in the dorsal part of the disc via a positive feedback loop involving the ETS transcription factor Pointed P2 (PntP2). The expression of vn in the ventral part of the disc is limited by the inhibitory effect of Wg and the restriction of pntP2 expression. A gene regulatory network (GRN), involving Vn, Dpp and Wg signaling pathways, is crucial for the patterning of the early wing disc. The GRN sub-circuit, which regulates early wing disc development, is essential for Drosophila wing and body wall development and it will be important to determine if this GRN sub-circuit is conserved in other insects.
Amanda Simcox (Advisor)
205 p.
Biochemistry; Bioinformatics; Biology; Genetics; Molecular Biology
Drosophila, RNase P, RNase MRP, Ribonucleoprotein complex, Intron, Development, Wing disc, Dpp, Vn, Wg,Gene regulatory network, Pnt P2, ETS

Recommended Citations

Citations

  • Manivannan, S. N. (2015). TRANSCRIPTIONAL CONTROL OF AN ESSENTIAL RIBOZYME AND AN EGFR LIGAND REVEAL SIGNIFICANT EVENTS IN INSECT EVOLUTION [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1437053490

    APA Style (7th edition)

  • Manivannan, Sathiya. TRANSCRIPTIONAL CONTROL OF AN ESSENTIAL RIBOZYME AND AN EGFR LIGAND REVEAL SIGNIFICANT EVENTS IN INSECT EVOLUTION. 2015. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1437053490.

    MLA Style (8th edition)

  • Manivannan, Sathiya. "TRANSCRIPTIONAL CONTROL OF AN ESSENTIAL RIBOZYME AND AN EGFR LIGAND REVEAL SIGNIFICANT EVENTS IN INSECT EVOLUTION." Doctoral dissertation, Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1437053490

    Chicago Manual of Style (17th edition)

osu1437053490
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© 2015, some rights reserved.Creative Commons License TRANSCRIPTIONAL CONTROL OF AN ESSENTIAL RIBOZYME AND AN EGFR LIGAND REVEAL SIGNIFICANT EVENTS IN INSECT EVOLUTION by Sathiya Narayanan Manivannan is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by The Ohio State University and OhioLINK.