The regulation and function of post-transcriptional RNA splicing

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. Post-transcriptional splicing has emerged as a key layer of gene expression regulation but is challenging to differentiate from co-transcriptional splicing. The authors review methodologies to detect post-transcriptional splicing, the mechanisms controlling splicing timing and how the temporal regulation of splicing affects gene expression.