Date of Award

Spring 5-2021

Document Type

Honors Thesis

Degree Name

Bachelor of Science

Department

Biological Science

Advisor/Committee Chair

Thomas Begley

Committee Member

Cara Pager

Abstract

Translation is a key step in protein synthesis in which the codons in messenger RNA (mRNA) are decoded by the corresponding anticodon in transfer RNA (tRNA). Prior to translation, tRNAs are modified by epitranscriptomic writers in order to ensure accurate decoding. During the previous semesters, different strains of Escherichia coli (E. coli) were used where genes corresponding to a tRNA modification enzyme were deleted from the genome. These strains were from the Keio E. coli gene deletion library and included the epitranscriptomic writers: CmoA, CmoB, Tgt, MnmE, QueA, ThiL, MnmC and TtcA. These strains were used to test the role of tRNA modifications in protein synthesis during the stress response to the antibiotic chloramphenicol (CAM). E.coli cells lacking the tRNA modification writers: selU, cmoA, cmoB, tgt, queA, thiL, mnmC ttcA and mnmE showed CAM sensitivity. The database Modomics was also used to identify RNA modifications and epitranscriptomic writers specific to the anticodon loops of tRNA from E. coli and humans. Then BLAST analysis was used to identify human homologs. Lastly, 27 human writers were analyzed for their links to cancer using The Cancer Genome Atlas and cBioportal database. Various cancers were identified that have amplifications in 5 of more writers and could be predicted to have changes in their epitranscriptome and may be addicted to these RNA modifications to promote translation. The human epitranscriptomic modifications: ALRYEF, CDKAL1, FTSJ1, GTPBP3, METTL11B, METTL18, METTL23 and METTL24 were found to have high levels of alteration frequencies for specific cancer types, with Bladder/ Urinary Tract cancer and Uterine Serous Carcinoma/ Uterine Papillary Serous Carcinoma cancers the most pronounced.

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