Date of Award
Doctor of Philosophy (PhD)
Non-co-linear RNAs, including circular and chimeric RNAs, have been investigated in a broad range of cellular processes and various diseases. The current biogenesis models of circular and chimeric RNAs depend on RNA splicing mechanisms. We hypothesized that some of the non-co-linear RNAs are products of an alternative mechanism other than RNA splicing. To test this hypothesis, we developed a method, which is independent of genome annotations and splicing signals, to identify Circular and Chimeric RNAs of All Types (C2AT or CAT for simplicity) by analyzing the RNA species profiled by whole genome RNA sequencing. Statistical analysis and experimental validation revealed that both circular RNAs (circRNAs) and chimeric RNAs may arise from the interior regions of exons and introns across the human genome, supporting a potential novel mechanism of biogenesis of circular and chimeric RNAs. Moreover, analysis of differential expressions of circRNAs and chimeric RNAs and their host genes suggested that these non-co-linear RNAs may play an important role in complex diseases, such as cancer and psoriasis. All the results from this systematic study of non-co-linear RNAs significantly expanded our understanding of the origin, diversity, and complexity of circRNAs and chimeric RNAs as well as their potential functions in complex diseases.
Sharlee Climer, Tao Ju, Brendan Juba, Paul Shaw,
Available for download on Wednesday, November 13, 2024