RNA-mediated gene regulation is less evolvable than transcriptional regulation.
RNA-mediated gene regulation is less evolvable than transcriptional regulation.
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DOI：
10.1073/pnas.1719138115
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发表时间：
2018-04-10
影响因子：
11.1
通讯作者：
Wagner A
中科院分区：
文献类型：
--
作者：
Payne JL;Khalid F;Wagner A
细胞以多种方式调节基因的活性。例如，它们通过称为转录因子的DNA结合蛋白调节转录，并且它们通过RNA结合蛋白调节mRNA稳定性和加工。根据目前的知识，转录调控是更广泛的，并参与了许多进化适应比转录后调控。原因可能是转录调控的研究更加深入。相反，我们认为转录调控具有内在的进化优势：当突变改变转录调控时，它们更有可能产生新的调控模式。也就是说，转录调控更容易进化。我们的分析表明了一个原因，为什么一种特定的基因调控在生物世界中特别丰富。大部分基因调控是由蛋白质结合DNA或RNA分子的特定序列进行的。一类这样的蛋白质是转录因子，其结合短DNA序列以调节转录。另一类是RNA结合蛋白，其结合短RNA序列以调节RNA成熟、转运和稳定性。在这里，我们研究这些监管机制的鲁棒性和可进化性。为此，我们使用172个人类和果蝇转录因子和RNA结合蛋白的实验结合数据以及人类多态性数据来研究体内结合位点的演变。我们发现调节蛋白-RNA相互作用和转录因子-DNA相互作用对DNA突变的鲁棒性之间没有什么区别。相比之下，我们发现RNA介导的调控比转录调控更不易进化，因为突变不太可能产生RNA分子与新RNA结合蛋白的相互作用，而不是产生基因调控区与新转录因子的相互作用。我们的观察结果与RNA结合蛋白与其靶分子之间的相互作用以及转录因子结合的调控区的进化可塑性所观察到的高水平的保守性是一致的。它们可能有助于解释为什么转录调控比RNA介导的基因调控涉及更多的进化适应和创新。
Cells regulate the activity of genes in a variety of ways. For example, they regulate transcription through DNA binding proteins called transcription factors, and they regulate mRNA stability and processing through RNA binding proteins. Based on current knowledge, transcriptional regulation is more widespread and is involved in many more evolutionary adaptations than posttranscriptional regulation. The reason could be that transcriptional regulation is studied more intensely. We suggest instead that transcriptional regulation harbors an intrinsic evolutionary advantage: when mutations change transcriptional regulation, they are more likely to bring forth novel patterns of such regulation. That is, transcriptional regulation is more evolvable. Our analysis suggests a reason why a specific kind of gene regulation is especially abundant in the living world. Much of gene regulation is carried out by proteins that bind DNA or RNA molecules at specific sequences. One class of such proteins is transcription factors, which bind short DNA sequences to regulate transcription. Another class is RNA binding proteins, which bind short RNA sequences to regulate RNA maturation, transport, and stability. Here, we study the robustness and evolvability of these regulatory mechanisms. To this end, we use experimental binding data from 172 human and fruit fly transcription factors and RNA binding proteins as well as human polymorphism data to study the evolution of binding sites in vivo. We find little difference between the robustness of regulatory protein–RNA interactions and transcription factor–DNA interactions to DNA mutations. In contrast, we find that RNA-mediated regulation is less evolvable than transcriptional regulation, because mutations are less likely to create interactions of an RNA molecule with a new RNA binding protein than they are to create interactions of a gene regulatory region with a new transcription factor. Our observations are consistent with the high level of conservation observed for interactions between RNA binding proteins and their target molecules as well as the evolutionary plasticity of regulatory regions bound by transcription factors. They may help explain why transcriptional regulation is implicated in many more evolutionary adaptations and innovations than RNA-mediated gene regulation.
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影响因子：
64.5
作者：
Cooper TA;Wan L;Dreyfuss G
通讯作者：
Dreyfuss G
DOI：
10.1126/science.1162327
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badis G;Berger MF;Philippakis AA;Talukder S;Gehrke AR;Jaeger SA;Chan ET;Metzler G;Vedenko A;Chen X;Kuznetsov H;Wang CF;Coburn D;Newburger DE;Morris Q;Hughes TR;Bulyk ML
通讯作者：
Bulyk ML
影响因子：
46.9
作者：
Berger, Michael F.;Philippakis, Anthony A.;Bulyk, Martha L.
通讯作者：
Bulyk, Martha L.
影响因子：
48
作者：
Isakova, Alina;Groux, Romain;Deplancke, Bart
通讯作者：
Deplancke, Bart
影响因子：
30.8
作者：
Cao, Qin;Anyansi, Christine;Yip, Kevin Y.
通讯作者：
Yip, Kevin Y.