Discovering the pathways and GO terms associated with Mettl3 modified circular RNAs in the embryonic cerebral cortex of mice.

Abstract

Circular RNAs (cirRNAs) are a class of RNA molecules that result from the alternative back-splicing events that join the 3’ and 5’ ends normally present in the linear RNA molecules. It has been published that cirRNAs can function as gene regulators and as “microRNA sponges” to negatively control the functions of microRNAs. While many studies have been conducted to understand the regulatory roles of Mettl3 in linear messenger RNAs, fewer contributions were applied to understand the impact of Mettl3 modified cirRNAs on gene expression and on the regulation of different KEGG biological pathways and GO terms. This thesis was conducted to identify the role of Mettl3 modification of cirRNAs in regulating gene expression and controlling different KEGG biological pathways and GO terms in the embryonic cerebral cortex of mice using high-throughput data sequencing. We constructed a generalized framework that led us to the identification of the cirRNA sequences that are significantly enriched in miRNA binding motifs and ultimately to the associated KEGG pathways and GO terms related to these interactions. It has been found by this study that Mettl3 modification in cirRNAs can regulate gene expression by controlling different KEGG biological pathways and GO terms in a manner that is similar, but not identical, to their corresponding linear mRNAs. While some KEGG pathways and GO terms appeared to be regulated by the Mettl3 modification of both linear mRNAs and cirRNAs, few GO terms were regulated in mRNAs but not in cirRNAs. Interestingly, it has been found that Mettl3 modification in cirRNAs can promote the regulation of unique KEGG biological pathways and GO processes (not being regulated by the Mettl3 modified mRNAs) that are significant to the regulation of the neurological diseases’ progressions such as brain tumors and intellectual disabilities in the embryonic cerebral cortex of mice.