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.

Committee Chair

Sergej Djuranovic

Committee Members

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

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Molecular Microbiology & Microbial Pathogenesis)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

Winter 1-15-2021

Language

English (en)

Author's ORCID

http://orcid.org/0000-0001-8802-635X

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