The role of circular RNAs in the evolution of the brain

Abstract

Current comprehension of circRNAs is relatively limited as compared to the extensive body of research available on other well-known coding and non-coding RNAs. CircRNAs have been implicated in gene regulatory functions and have been reported to display endogenous translational capacities. Current research demonstrates the conservation of circRNAs in mammalian brains, with humans having the most complex circular transcriptome currently known. In addition, expanding circular transcriptomes in ageing brains demonstrates the increase in circular network complexity alongside increasing complexity in maturing brain neural networks. Combined, the lack of knowledge of circRNAs could prove to be an understudied, and potentially fundamental, basis for the comprehension of brain evolution through time and amongst species. This research identified four conserved circRNAs between human and mouse cortex where 760 and 60 circRNAs had been discovered respectively; a fact that is indicative not only of some level of circular conservation between the mammalian brains, but also the potential impact of the independent circular transcriptomes on the evolution of the human brain as it is known today. The common circular transcriptome determined in human oligodendrocytes and neurons indicates a moderately interconnected basis of brain function and development; however, the distinct differences in cirexons being predominantly already annotated linear mRNA exons in the human cortex, compared to the high proportion of intronic/intergenic circRNA fragments comprising cirexons in human cell lines, could provide a novel distinct comprehension of human brain function and evolution through time. Current research of circRNA functions have not yielded results that provide a substantive understanding of their function. To the extent that this understanding remains elusive, it provides an incomplete foundation upon which to base interpretations of the reults from this research. Nevertheless, what is distinct is the increase in circRNAs in human brains and the postulated role of circRNAs being gene regulators, implicating circRNAs as definitive in human brain evolution with regard to functional capacity and complexity as compared to other mammals.