White, Brian Andrew (2019-08). Beyond the Liaison: Exploring Novel Insights Into the Genomic Distribution of tRNA and tRNA-Mediated Transcriptional and Translational Regulation. Master's Thesis.
Transfer RNAs (tRNAs) are primeval molecules ubiquitous to all domains of life. The interactions between aminoacyl-tRNAs (aa-tRNAs) and actively translating ribosomes are critical components to the central dogma of biology as they are directly involved in the transformation of genetic code into protein. It is generally believed that this limited interaction is the extent of cooperation between tRNAs and protein-coding transcripts, however, recent findings suggest this relationship is much more complex. Using robust computational methods, we identify intact tRNA genes that intersect 79 protein-coding genes, 30 long intergenic non-coding RNA genes (lincRNA), and 11 antisense genes, among other gene types. A tRNA sequence that overlaps the interval of another gene is likely to solicit fundamental aspects of tRNA biology to the overlapped gene where they are otherwise not expected. Here, we present the hypothesis that when the interval of a tRNA gene is found to overlap the interval of another gene, the tRNA gene will introduce regulatory mechanisms that affect both the transcription and translation of the overlapped gene by various processes normally associated with tRNA biology. Furthermore, we describe an uneven distribution of tRNA genes in the human genome that reveals an acute concentration of tRNA genes that cluster with regions related to nucleosome assembly and the major histocompatibility complex (MHC). Our findings highlight the possibility that overlapping tRNA genes play a role in the transcriptional and post-transcriptional regulation of overlapped genes and these overlaps affect previously undescribed mechanisms of transcriptional and translational regulation. Moreover, the identified clustering of tRNA genes with regions associated with nucleosome assembly and the MHC suggests tRNA biology may facilitate necessary processes to histone organization and adaptive immunology.