2024 May ; 629(8014): 1165–1173 | Prashant Bhat, Amy Chow, Benjamin Emert, Olivia Ettlin, Sofia A. Quinodoz, Mackenzie Strehle, Yodai Takei, Alex Burr, Isabel N. Goronzy, Allen W. Chen, Wesley Huang, Jose Lorenzo M. Ferrer, Elizabeth Soehalim, Say-Tar Goh, Tara Chari, Delaney K. Sullivan, Mario R. Blanco, Mitchell Guttman
The study investigates the role of nuclear speckles in mRNA splicing efficiency. Nuclear speckles are defined by high concentrations of protein and noncoding RNA regulators of pre-mRNA splicing. The research shows that genes located near nuclear speckles exhibit higher spliceosome concentrations, increased spliceosome binding to pre-mRNAs, and higher co-transcriptional splicing levels compared to genes farther from speckles. The proximity of genes to speckles is dynamic between cell types and changes in speckle proximity lead to differences in splicing efficiency. Directed recruitment of pre-mRNAs to nuclear speckles increases mRNA splicing levels. These findings integrate long-standing observations of nuclear speckles with the biochemistry of mRNA splicing, suggesting that the spatial organization of genomic DNA around nuclear speckles drives spliceosome concentrations and controls splicing efficiency.The study investigates the role of nuclear speckles in mRNA splicing efficiency. Nuclear speckles are defined by high concentrations of protein and noncoding RNA regulators of pre-mRNA splicing. The research shows that genes located near nuclear speckles exhibit higher spliceosome concentrations, increased spliceosome binding to pre-mRNAs, and higher co-transcriptional splicing levels compared to genes farther from speckles. The proximity of genes to speckles is dynamic between cell types and changes in speckle proximity lead to differences in splicing efficiency. Directed recruitment of pre-mRNAs to nuclear speckles increases mRNA splicing levels. These findings integrate long-standing observations of nuclear speckles with the biochemistry of mRNA splicing, suggesting that the spatial organization of genomic DNA around nuclear speckles drives spliceosome concentrations and controls splicing efficiency.