ORCID
http://orcid.org/0000-0001-8802-635X
Date of Award
Winter 1-15-2021
Degree Name
Doctor of Philosophy (PhD)
Degree Type
Dissertation
Abstract
The process of protein synthesis whereby a messenger RNA is decoded into an amino acid chainis conserved among the domains. Fastidious protein synthesis is necessary for organism survival. However, exceptions negatively affecting the mRNA translation cycle – inadvertently or by design – may occur. Polyadenosine tracts are one such motif causing ribosomal stalling and frameshifting in almost all organisms tested thus far; save Plasmodium spp. Thus, with ~60% of their protein-coding genome harboring polyadenosine tracts, the elucidation of such paradigm-breaking adaptations enabling Plasmodium spp. to translate this typically problematic motif without issue is salient from both basic science and clinical perspectives. Using biochemical and structural approaches, I report on the parasite ability to express polyA motifs and ribosome alterations enabling polylysine synthesis. The developed PP7-mRIP assay reveals RBP differences among varying mRNA substrates, revealing a previously uncharacterized, parasite-specific AU-rich binding protein bound to polyA tract reporter mRNA. Finally, the parasite exhibits altered binding of the essential ribosomal protein RACK1, vital for translation cap-dependent initiation and quality control activation, that would invariably alter ribosome- associated quality control pathway signaling, ostensibly aiding polyA translation.
Language
English (en)
Chair and Committee
Sergej Djuranovic
Committee Members
Daniel Goldberg, Sebla Kutluay, L. D. Sibley, Hani Zaher,
Recommended Citation
Erath, Jessey Lee, "Protein Synthesis Adaptation to the AU-Rich Transcriptome of Plasmodium falciparum" (2021). Arts & Sciences Electronic Theses and Dissertations. 2363.
https://openscholarship.wustl.edu/art_sci_etds/2363