Spliceosomal introns are non-coding DNA sequences interspersed between exons in eukaryotic genes. While most are removed post-transcriptionally by RNA splicing and do not encode proteins, they have been implicated in various regulatory processes, including gene transcription, mRNA nuclear export, and the generation of protein diversity. Despite their widespread presence and regulatory roles, the essentiality of spliceosomal introns for fundamental cellular life has long remained an open question.
In a study published in Cell, a research team led by Professor ZHOU Jinqiu from the Center for Excellence in Molecular Cell Science (Shanghai Institute of Biochemistry and Cell Biology) of the Chinese Academy of Sciences, successfully constructed a yeast strain—named SYNE27α—in which all 300 known spliceosomal introns were systematically eliminated. This work was built upon a single‑chromosome yeast strain previously developed in 2018 by Professor QIN Zhongjun's research team at the Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences. The viability of this intron‑free strain demonstrates that spliceosomal introns are not essential for yeast survival.
To overcome the technical challenge of deleting 300 introns sequentially—a process that would have taken an estimated 12 years—the team devised a strategy combining parallel intron deletions in haploids of opposite mating types, followed by site‑specific chromosomal recombination in diploids and meiotic segregation to recover haploid progeny carrying all desired deletions. This approach reduced the timeline to approximately six years. Whole‑genome sequencing confirmed the precise removal of all 300 introns across 288 genes in SYNE27α.
Although the cumulative loss of all introns resulted in a slow‑growth phenotype—primarily attributable to ribosomal dysregulation—the SYNE27α strain remained stable and could be continuously passaged under standard laboratory conditions. Importantly, heterozygous diploid cells (SY14/SYNE27α), which carry a single copy of the intron‑free genome, grew normally, indicating that the fitness defects associated with intron loss are recessive.
In a striking further finding, the researchers showed that deleting genes encoding core spliceosomal components—including the splicing factors LUC7, YHC1, PRP8, PRP9, and PRP19, as well as the five snRNAs (U1, U2, U4, U5, and U6)—did not compromise the viability of SYNE27α. These results provide compelling evidence that the primary and essential function of the spliceosome is to process spliceosomal introns, rather than to carry out other proposed non‑splicing roles, such as transcription‑coupled splicing or nucleocytoplasmic transport.
The SYNE27α strain represents the first eukaryotic model entirely devoid of spliceosomal introns. It not only marks a key step toward genome streamlining and the construction of minimal eukaryotic genomes, but also provides a unique experimental platform for studying the molecular mechanisms of pre‑mRNA and snoRNA splicing, the evolution of introns, and the principles underlying eukaryotic gene expression regulation.
Reference: https://www.cell.com/cell/abstract/S0092-8674(26)00624-0
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