The human transcriptome comprises >80 000 protein-coding transcripts and the estimated number of proteins synthesized from these transcripts is in the range of 250 000 to 1 million. These transcripts and proteins are encoded by less than 20 000 genes, suggesting extensive regulation at the transcriptional, post-transcriptional, and translational level. Here we review how RNA sequencing (RNA-seq) technologies have increased our understanding of the mechanisms that give rise to alternative transcripts and their alternative translation. The authos highlight four different regulatory processes: alternative transcription initiation, alternative splicing, alternative polyadenylation, and alternative translation initiation. They discuss their transcriptome-wide distribution, their impact on protein expression, their biological relevance, and the possible molecular mechanisms leading to their alternative regulation. They conclude with a discussion of the coordination and the interdependence of these four regulatory layers.
What we’ve learned:
- RNA sequencing can uncover the mechanisms regulating gene expression.
- Use of alternative TSSs, PASs, and exons is the rule.
- Alternative translation initiation at 5′-UTRs and downstream codons is widespread.
- Transcription, RNA processing, and translation are often interdependent processes.