A wide variety of post-transcriptional regulatory events in the life of an mRNA have emerged as major checkpoints during its temporal and spatial journey within the cell. The advent of deep sequencing technologies combined with various fractionation or enrichment protocols has produced a wealth of data regarding transcripts, their variants and their interactomes. Yet, these data must be integrated with mechanistic and biological frameworks in order to better understand complex and dynamic regulatory networks that tailor mRNA metabolism and shape the cell proteome in healthy and diseased states.