Manny Ares, a distinguished professor at UC Santa Cruz, has been dedicated to unraveling the mysteries of RNA splicing throughout his career. Introns, DNA sequences that interrupt protein-coding information in genes, are removed by the spliceosome, a specialized RNA protein complex. Ares’s recent discovery, published in Genes and Development, indicates that the spliceosome may have the ability to reinsert introns back into the genome. This finding challenges previous beliefs about the limitations of spliceosomes and sheds light on the evolution of different species and the adaptation of cells to the presence of introns.
The two-step process of intron removal by the spliceosome results in the formation of circular structures known as lariat introns. Researchers observed circular introns in addition to the typical lariat form, sparking Ares’s interest in possible interactions between the spliceosome and introns post-splicing. Given the similarities between the chemical mechanisms of spliceosomes and Group II introns, it is theorized that they share a common ancestor responsible for spreading introns in genomes. Ares’s investigation into the spliceosome’s ability to reshape introns post-splicing revealed its potential to catalyze the reinsertion of introns into the genome, hinting at an ancestral function still present in modern cells.
Further experiments are planned to confirm the spliceosome’s capability to insert introns into DNA by creating artificial conditions in which lariat introns are presented to the spliceosome for reinsertion. While this process may be rare in humans due to the high demand for spliceosomes, organisms with less busy spliceosomes may experience more frequent intron reinsertion events. A collaboration between Ares and UCSC Biomolecular Engineering Professor Russ Corbett-Detig aims to investigate intron “burst” events in evolutionary history that introduced numerous introns into genomes simultaneously. This interdisciplinary partnership allows for a deeper exploration of the complexities of introns and genome evolution.
The potential reinsertion of introns by spliceosomes could offer valuable insights into the evolution of genetic information processing in organisms. By studying how genomes react to bursts of intron insertions, researchers like Ares and Corbett-Detig hope to gain a better understanding of the mechanisms driving genomic complexity. Their collaborative approach leverages diverse expertise and perspectives to tackle complex scientific challenges and uncover the secrets of intron evolution. This ongoing research holds promise for expanding our knowledge of RNA splicing processes and the intricate interplay between genes and proteins in living organisms.