Introns are stretches of non-coding regions interspersed with the coding DNA in the genes of eukaryotic organisms. They are widespread, common and sometimes are ridiculously long stressing the economy of the cell. Burden of long introns is not limited to DNA replication which happens only once during cell division but continues to manifest itself at the transcription level where multiple rounds of RNA polymerase II activity consume energy proportional to the longevity of the cell. For instance, the 2.3 Gb Human dystrophin (DMD) gene contains 78 introns and takes a whopping 16 hours to transcribe. Similarly the U3 small nucleolar RNA-associated protein 11 (UTP11) in sugar pine has disproportionately long introns. The coding part of 849,085 bp long UTP 11 is only 699 bp. In contrast, the introns add up to 848,386 bp.
This short film by the Nature Magazine explains the esoteric intron concept in a quite creative abstract way for those people who are old enough to know what a cassette tape and a walkman are. So here is another short video from HHMI that explains how introns are spliced out of the mRNA during gene transcription, the first step of the Central Dogma of biology:
Intron evolution has a long standing debate between “introns early” and “introns late” camps. Introns early hypothesis suggests introns are ancient possibly going as far back as the RNA World
but are gradually being eliminated from eukaryotic genomes. Alternatively, introns late hypothesis suggests that these structures evolved relatively recently and are being accumulated in coding regions.
What could be the selective advantage of having long introns? The topological landscape of the chromatin is complex requiring long-range interactions among cis-regulated elements. Such long-range interactions could be mediated by introns bringing associated domains such as enhancers and promoters in close proximity. Techniques such as 3C (Chromatin Conformation Capture) sequencing is now allowing a three dimensional understanding of the genomes. Gene looping mediated by long introns could be a way to recycle RNA Pol II by introns of sufficient length bringing 5’ and 3’ ends of a gene together. Now evidence coming from Yeast is adding a new dimension to potential functions of introns.
Two independent intron deletion experiments in Yeast have revealed that retention of excised introns forming physical complexes with the spliceosome increased survival rates. Loss of introns in Yeast leads to unchecked production of ribosomal proteins in nutrient limited conditions due to deregulation of TORC1-mediated inhibition. Target of Rapamycin was first detected in mammals but now we know that the entire pathway is conserved in all eukaryotes including plants, animals and fungi.
In nature stress is prevalent. By testing importance of introns under nutrient-poor conditions researchers have established a real life scenario. The evidence is compelling that introns influence the RNA populations in cells via a highly central integrator of nutrients: TOR. Intron size and numbers in Yeast are quite small. Now the exciting quest is to check out other organisms like gymnosperms such as the sugar pine (Pinus lambertiana) with Giga-genomes who carry massive introns.
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