Post-transcriptional regulatory networks play a key role in noise reduction that is conserved from micro-organisms to mammals
Post-transcriptional regulatory networks play a key role in noise reduction that is conserved from micro-organisms to mammals
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DOI：
10.1111/j.1742-4658.2012.08571.x
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发表时间：
2012-09-01
期刊：
影响因子：
5.4
通讯作者：
Michoel, Tom
中科院分区：
文献类型：
--
作者：
Joshi, Anagha;Beck, Yvonne;Michoel, Tom
RNA结合蛋白（RBP）是原核生物和真核生物中mRNA转录稳定性和翻译的核心调节因子。酵母全基因组研究表明，RBP的表达动力学，RBP-mRNA结合相互作用的转录后调控网络的结构和转录后调控的表达谱中的噪音减少之间存在有趣的关系。在本研究中，我们组装和比较的基因组特性的RBPs和集成的转录和转录后调控网络在四个物种：大肠杆菌，酵母，小鼠和人类。我们发现，RBP始终受到调节，以具有最低水平的蛋白质噪音，已知的噪音缓冲网络基序在整合的网络中富集，转录后反馈回路作为其他监管机构的监管机构。这些结果支持了一个一般模型，其中RBP是许多下游细胞过程中随机噪声缓冲的关键调节器。目前可用的数据集不允许澄清RBP和非编码RNA的转录后调节是否起着相似或不同的作用，尽管我们发现了转录因子，RBP和micro-RNA的特定组合共同调节人类已知疾病途径的证据，这表明两种转录后调节模式之间的互补性而不是冗余性。
RNA-binding proteins (RBPs) are core regulators of mRNA transcript stability and translation in prokaryotes and eukaryotes alike. Genome-wide studies in yeast have shown intriguing relationships between the expression dynamics of RBPs, the structure of post-transcriptional regulatory networks of RBP-mRNA binding interactions and noise reduction in post-transcriptionally regulated expression profiles. In the present study, we assembled and compared the genomic properties of RBPs and integrated transcriptional and post-transcriptional regulatory networks in four species: Escherichia coli, yeast, mouse and human. We found that RBPs are consistently regulated to have minimal levels of protein noise, that known noise-buffering network motifs are enriched in the integrated networks and that post-transcriptional feedback loops act as regulators of other regulators. These results support a general model where RBPs are the key regulators of stochastic noise-buffering in numerous downstream cellular processes. The currently available datasets do not allow clarification of whether post-transcriptional regulation by RBPs and by noncoding RNAs plays a similar or distinct role, although we found evidence that specific combinations of transcription factors, RBPs and micro-RNAs jointly regulate known disease pathways in humans, suggesting complementarity rather than redundancy between both modes of post-transcriptional regulation.