Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), 20139 Milan, Italy.
Brief Bioinform. 2021 Jul 20;22(4). doi: 10.1093/bib/bbaa389.
Despite gene expression programs being notoriously complex, RNA abundance is usually assumed as a proxy for transcriptional activity. Recently developed approaches, able to disentangle transcriptional and post-transcriptional regulatory processes, have revealed a more complex scenario. It is now possible to work out how synthesis, processing and degradation kinetic rates collectively determine the abundance of each gene's RNA. It has become clear that the same transcriptional output can correspond to different combinations of the kinetic rates. This underscores the fact that markedly different modes of gene expression regulation exist, each with profound effects on a gene's ability to modulate its own expression. This review describes the development of the experimental and computational approaches, including RNA metabolic labeling and mathematical modeling, that have been disclosing the mechanisms underlying complex transcriptional programs. Current limitations and future perspectives in the field are also discussed.
尽管基因表达程序众所周知非常复杂，但 RNA 丰度通常被视为转录活性的替代物。最近开发的方法能够区分转录和转录后调控过程，揭示了更为复杂的情况。现在可以弄清楚合成、加工和降解动力学速率如何共同决定每个基因 RNA 的丰度。现在已经清楚的是，相同的转录输出可以对应于不同的动力学速率组合。这突出表明，存在明显不同的基因表达调控模式，每种模式都对基因自身调节表达的能力产生深远影响。这篇综述描述了实验和计算方法的发展，包括 RNA 代谢标记和数学建模，这些方法揭示了复杂转录程序的潜在机制。还讨论了该领域当前的局限性和未来的展望。
