Yoseop Yoon, Chang Quan, Lindsey V. Soles, Yongsheng Shi
mRNA maturation requires precise coordination among transcription, 5' capping, splicing, and 3' end formation. Recent biochemical, structural, and genomic studies demonstrate that these processes are tightly coupled through dynamic interactions among RNA polymerase II, the spliceosome, and cleavage-polyadenylation complexes. Here, we synthesize current mechanistic insights into how transcription elongation factors and RNA processing machineries communicate to ensure efficient and accurate transcript maturation. We propose a "U1 relay" model as a unified framework for understanding co-transcriptional splicing and 3' end formation. We further discuss how RNAs are sorted into nuclear retention/degradation or export pathways based on the RNA processing status. Importantly, RNA processing factors not only act downstream of transcription but also feed back to modulate transcriptional elongation, pausing, and termination, thereby reinforcing bidirectional coupling between RNA synthesis and processing.