Introns, once dismissed as “junk” RNA, impose a significant energetic cost to transcribe, remove, and degrade, suggesting they confer an evolutionary advantage. While introns regulate splicing, transport, and degradation within their host pre-mRNAs, their broader role remains an area of active exploration. In human cells, alternative splicing allows a single gene to produce multiple proteins, and our lab has shown that reprogrammed splicing in breast and ovarian cancers may serve as a cancer marker. However, the conservation of introns in organisms like yeast, which lack alternative splicing, points to additional critical functions. Our research has revealed that introns in yeast play a vital role in helping cells survive starvation by modulating spliceosomal components in a TOR-dependent manner, favoring the splicing of meiotic genes and repressing ribosomal protein genes. This discovery redefines introns as key regulators of cellular function across genes and pathways. To uncover the fundamental reasons behind intron conservation and their role in shaping the global transcriptome landscape, we aim to create the first splicing-free eukaryotic cells. This groundbreaking model will allow us to investigate how intron loss impacts essential processes like stress resistance, drug tolerance, and nutrient deprivation. Since splicing components and the TOR sensing pathway are highly conserved between yeast and humans, this research promises to transform our understanding of intron functions in both simple and complex organisms. By uncovering the fundamentals of splicing regulation and intron function, we aim to facilitate the construction of synthetic genomes and open new avenues for therapeutic strategies targeting diseases caused by disrupted RNA processing and splicing regulation.
