Dynamics of RNA localization to nuclear speckles are connected to splicing efficiency

Dynamics of RNA localization to nuclear speckles are connected to splicing efficiency

16 October 2024 | Jinjun Wu, Yu Xiao, Yuzheng Liu, Li Wen, Chuanyang Jin, Shun Liu, Sneha Paul, Chuan He, Oded Regev, Jingyi Fei
RNA localization to nuclear speckles is closely linked to splicing efficiency. Using ARTR-seq, researchers identified three groups of genes based on transcript localization to nuclear speckles: group A genes with stably enriched transcripts, group B genes with transiently enriched transcripts at the pre-mRNA stage, and group C genes with no enrichment. Stably enriched transcripts contain inefficiently excised introns, and nuclear speckle disruption affects splicing of these transcripts. RNA sequence features contribute to transcript localization, indicating a tight interplay between transcript enrichment, genome organization, and splicing efficiency. Nuclear speckles regulate both co- and posttranscriptional splicing. Genes with stably enriched transcripts are over-represented among genes with heat shock-up-regulated intron retention, suggesting a connection between speckle localization and cellular stress response. Nuclear speckles are membraneless organelles involved in gene expression, containing splicing factors and a rich transcriptome. Changes in speckle composition are associated with diseases. Speckles are active hubs promoting gene expression, with gene foci often localized near speckles. Speckles accommodate posttranscriptionally accumulated transcripts and promote cotranscriptional splicing. They also facilitate splicing of stress-related genes and affect alternative splicing. However, the role of speckles in splicing remains unclear. ARTR-seq was used to map the nuclear speckle transcriptome. It identified three gene groups with different localization properties. Speckle-enriched transcripts contain unexcised introns, and splicing inhibition increases the fraction of unspliced transcripts in speckles. Transcripts demonstrate diverse dynamics in speckle localization, with group A transcripts stably enriched, group B transcripts transiently enriched, and group C transcripts not enriched. Speckle-enriched genes are enriched in RNA metabolism and nucleus localization, while non-speckle-enriched genes are enriched in extracellular organelles, membranes, and the endoplasmic reticulum. Transcript speckle enrichment is positively correlated with gene focus proximity to speckles. Speckle-enriched transcripts are more likely to be associated with gene foci near speckles. Speckle-enriched RNA foci are closer to speckles, while non-speckle-enriched RNA foci are not. Speckle-enriched transcripts are associated with transcription sites, while non-speckle-enriched transcripts are not. Speckle-enriched transcripts are weakly correlated with RNA abundance but strongly correlated with splicing timing and efficiency. Speckle-enriched transcripts with slow splicing kinetics and posttranscriptionally excised introns are more enriched in speckles. Nuclear speckles facilitate splicing of speckle-enriched transcripts. Disrupting speckles with siRNA knockdown of SON and SRRMRNA localization to nuclear speckles is closely linked to splicing efficiency. Using ARTR-seq, researchers identified three groups of genes based on transcript localization to nuclear speckles: group A genes with stably enriched transcripts, group B genes with transiently enriched transcripts at the pre-mRNA stage, and group C genes with no enrichment. Stably enriched transcripts contain inefficiently excised introns, and nuclear speckle disruption affects splicing of these transcripts. RNA sequence features contribute to transcript localization, indicating a tight interplay between transcript enrichment, genome organization, and splicing efficiency. Nuclear speckles regulate both co- and posttranscriptional splicing. Genes with stably enriched transcripts are over-represented among genes with heat shock-up-regulated intron retention, suggesting a connection between speckle localization and cellular stress response. Nuclear speckles are membraneless organelles involved in gene expression, containing splicing factors and a rich transcriptome. Changes in speckle composition are associated with diseases. Speckles are active hubs promoting gene expression, with gene foci often localized near speckles. Speckles accommodate posttranscriptionally accumulated transcripts and promote cotranscriptional splicing. They also facilitate splicing of stress-related genes and affect alternative splicing. However, the role of speckles in splicing remains unclear. ARTR-seq was used to map the nuclear speckle transcriptome. It identified three gene groups with different localization properties. Speckle-enriched transcripts contain unexcised introns, and splicing inhibition increases the fraction of unspliced transcripts in speckles. Transcripts demonstrate diverse dynamics in speckle localization, with group A transcripts stably enriched, group B transcripts transiently enriched, and group C transcripts not enriched. Speckle-enriched genes are enriched in RNA metabolism and nucleus localization, while non-speckle-enriched genes are enriched in extracellular organelles, membranes, and the endoplasmic reticulum. Transcript speckle enrichment is positively correlated with gene focus proximity to speckles. Speckle-enriched transcripts are more likely to be associated with gene foci near speckles. Speckle-enriched RNA foci are closer to speckles, while non-speckle-enriched RNA foci are not. Speckle-enriched transcripts are associated with transcription sites, while non-speckle-enriched transcripts are not. Speckle-enriched transcripts are weakly correlated with RNA abundance but strongly correlated with splicing timing and efficiency. Speckle-enriched transcripts with slow splicing kinetics and posttranscriptionally excised introns are more enriched in speckles. Nuclear speckles facilitate splicing of speckle-enriched transcripts. Disrupting speckles with siRNA knockdown of SON and SRRM
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