More than a splicing code: integrating the role of RNA, chromatin and non-coding RNA in alternative splicing regulation

Large portions of the genome undergo alternative pre-mRNA splicing in often intricate patterns. Alternative splicing regulation requires extensive control mechanisms since errors can have deleterious consequences and may lead to developmental defects and disease. Recent work has identified a complex network of regulatory RNA elements which guide splicing decisions. In addition, the discovery that transcription and splicing are intimately coupled has opened up new directions into alternative splicing regulation. Work at the interface of chromatin and RNA biology has revealed unexpected molecular links between histone modifications, the transcription machinery, and non-coding RNAs (ncRNAs) in the determination of alternative splicing patterns.

► Regulation of alternative pre-mRNA splicing is multifactorial. ► Splicing is coupled to transcription and modulated by RNAP II elongation rate. ► Chromatin structure and histone modifications regulate alternative splicing. ► Epigenetic information is transmitted to RNA via chromatin-splicing adaptor complexes. ► Non-coding RNAs are emerging as new regulators of alternative splicing.