A protein complex have been found to change regulation of genes in human brain cells.
Humans develop a very complex brain organ with specific structures and connections, yet we do not have much more genes than organisms with simple nervous systems. This exceptional quality is attributed to the sophisticated structure of our genes: every gene consists of distinct blocks (called exons) which can be shuffled, excluded, included or even divided in many combinations. One gene can lead to dozens of different outcomes. However, a mechanism governing exon combination, known as splicing, requires intricate regulation to maintain proper function of genes.
Exon Junction Complex (EJC) is one of the agents influencing the regulation. Although it was discovered decades ago, there is still ongoing research showing its new modes of regulation.
A new function of exon junction complex is an arrest of recursive splicing events. In contrast to standard splicing, recursive splicing happens in a two-step process and allows to divide exons. A common example is an exclusion of the second half of an exon from a gene product. This exclusion is initially originating from a specific sequence (RS-5ss) recognized by splicing machinery. Exon junction complex helps to stop the exclusion.
Evolutionary-context analysis has provided interesting insights into this process. Exon junction complex is considerably less efficient in insects than in mammals. In mice and humans, exon junction complex is much more active, and the brain is essential organ benefiting from the mechanism. It might be possible that exon junction complex helped mammals to develop larger brains.
From a clinical perspective, the disruptions of any genes (RBM8A, EIF4A3, MAGOH) forming the complex leads to increased recursive splicing events and various brain disorders, like microcephaly. The study probably elucidated a precise mechanism which leads to some cases of nervous system disorders.
More: “Exon Junction Complex Shapes the Transcriptome by Repressing Recursive Splicing”, L. Blazquez et al., 2018, doi:10.1016/j.molcel.2018.09.033.