Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Trends Genet. 2015 Mar;31(3):128-39. doi: 10.1016/j.tig.2015.01.001. Epub 2015 Jan 30.
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. We highlight four different regulatory processes: alternative transcription initiation, alternative splicing, alternative polyadenylation, and alternative translation initiation. We discuss their transcriptome-wide distribution, their impact on protein expression, their biological relevance, and the possible molecular mechanisms leading to their alternative regulation. We conclude with a discussion of the coordination and the interdependence of these four regulatory layers.
人类转录组包含>80000 个编码蛋白质的转录本，这些转录本合成的蛋白质数量估计在 25 万到 100 万之间。这些转录本和蛋白质由不到 20000 个基因编码，这表明在转录、转录后和翻译水平存在广泛的调控。在这里，我们回顾了 RNA 测序 (RNA-seq) 技术如何提高我们对产生替代转录本及其替代翻译的机制的理解。我们强调了四个不同的调节过程：转录起始的替代、剪接的替代、多聚腺苷酸化的替代和翻译起始的替代。我们讨论了它们在转录组水平上的分布、对蛋白质表达的影响、它们的生物学相关性，以及导致它们替代调节的可能分子机制。最后，我们讨论了这四个调节层的协调和相互依存。
