Choquet Karine, Patop Ines L, Churchman L Stirling
Department of Biochemistry and Functional Genomics, University of Sherbrooke, Sherbrooke, Quebec, Canada.
Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Nat Rev Genet. 2025 Jun;26(6):378-394. doi: 10.1038/s41576-025-00836-z. Epub 2025 Apr 11.
Eukaryotic RNA transcripts undergo extensive processing before becoming functional messenger RNAs, with splicing being a critical and highly regulated step that occurs both co-transcriptionally and post-transcriptionally. Recent analyses have revealed, with unprecedented spatial and temporal resolution, that up to 40% of mammalian introns are retained after transcription termination and are subsequently removed largely while transcripts remain chromatin-associated. Post-transcriptional splicing has emerged as a key layer of gene expression regulation during development, stress response and disease progression. The control of post-transcriptional splicing regulates protein production through delayed splicing and nuclear export, or nuclear retention and degradation of specific transcript isoforms. Here, we review current methodologies for detecting post-transcriptional splicing, discuss the mechanisms controlling the timing of splicing and examine how this temporal regulation affects gene expression programmes in healthy cells and in disease states.
真核生物的RNA转录本在成为功能性信使RNA之前会经历广泛的加工过程,剪接是一个关键且受到高度调控的步骤,它既可以在转录过程中发生,也可以在转录后发生。最近的分析以前所未有的空间和时间分辨率揭示,高达40%的哺乳动物内含子在转录终止后会保留下来,随后在转录本仍与染色质相关时大部分被去除。转录后剪接已成为发育、应激反应和疾病进展过程中基因表达调控的关键层面。转录后剪接的控制通过延迟剪接和核输出,或特定转录本异构体的核滞留和降解来调节蛋白质的产生。在这里,我们综述了目前检测转录后剪接的方法,讨论了控制剪接时间的机制,并研究了这种时间调控如何影响健康细胞和疾病状态下的基因表达程序。