Date of Award

Winter 1-15-2021

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Microbiology & Microbial Pathogenesis)

Degree Name

Doctor of Philosophy (PhD)

Degree Type



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.


English (en)

Chair and Committee

Sergej Djuranovic

Committee Members

Daniel Goldberg, Sebla Kutluay, L. D. Sibley, Hani Zaher,