New beginnings

Cell 179, 1551–1565 (2019)

Credit: Cell Press

Alternative RNA splicing regulates gene expression by varying the inclusion of exons and introns in mRNAs. Fiszbein et al. have now defined a phenomenon called exon-mediated activation of transcription starts (EMATS), which reveals an association between exon splicing and transcriptional start. By comparing RNA transcripts from different species, the authors found that the inclusion of mouse-specific evolutionarily new exons is positively correlated with gene expression and gain of transcription start sites (TSSs). Repressing the splicing of new exons with morpholino antisense oligonucleotides or CRISPR–Cas9 mutations decreased exon inclusion and the expression levels of their parent genes. The proximal upstream TSS exhibited altered association with core transcription machinery, and further studies found that both 5′ and 3′ splice sites are essential for this mode of gene upregulation. These results suggest that new exons promote the creation of new promoters in the proximal upstream region. More importantly, the authors found that similar rules can also be generally applied to thousands of genes with skipped exons (SE); inclusion of SE promotes the usage of a weak proximal TSS. This study provides a good example of finding new insights based on known databases and new ideas for regulating gene expression.

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Correspondence to Yiyun Song.

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Song, Y. New beginnings. Nat Chem Biol 16, 106 (2020). https://doi.org/10.1038/s41589-020-0466-4

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