Janga Sarath Chandra, Babu M Madan
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK CB2 0QH.
Mol Biosyst. 2009 Feb;5(2):154-62. doi: 10.1039/b816845h. Epub 2008 Dec 9.
Gene expression is a dynamic process which can be controlled by a number of mechanisms as genetic information flows from nucleic acids to proteins. The study of gene expression in the steady state, while informative, overlooks the underlying dynamics of the processes. Steady-state transcript levels are a result of both RNA synthesis and degradation, and as such, measurements of degradation rates can be used to determine their rates of synthesis as well as reveal regulation that occurs via changes in RNA stability. Messenger RNA degradation plays a central role in diverse cellular processes and is controlled primarily by the activity of the degradosome in prokaryotes. In this study, we use the currently available network of protein-protein interactions (PPIs) and mRNA half-lives in Escherichia coli to demonstrate that centrality of a protein in the PPI network is strongly correlated with its mRNA half-life. We find that interacting proteins tend to show similar half-lives, commonly referred to as assortative behavior in networks, which is frequently found in biological and social networks. While a major fraction of the interacting proteins show significantly lower differences in mRNA stabilities, a smaller but significant number of protein pairs tend to show higher differences than expected by chance. Higher differences in transcript stabilities often involved those that encode for transcription factors and enzymes, suggesting a feedback link at the post-translational level. We also note that although essential genes, which act as a proxy for in vivo centrality in PPI networks, are highly expressed compared to non-essential ones, they do not encode for more stable transcripts than non-essential genes. Our results provide a direct link between mRNA stability and centrality of a protein in PPI network indicating the importance of post-transcriptional mechanisms on nascent RNAs in the cell.
基因表达是一个动态过程,随着遗传信息从核酸流向蛋白质,它可以由多种机制控制。对稳态下基因表达的研究虽然提供了信息,但忽略了这些过程潜在的动态变化。稳态转录水平是RNA合成和降解的共同结果,因此,降解速率的测量可用于确定其合成速率,以及揭示通过RNA稳定性变化发生的调控。信使RNA降解在多种细胞过程中起着核心作用,在原核生物中主要受降解体活性的控制。在本研究中,我们利用大肠杆菌中目前可用的蛋白质-蛋白质相互作用(PPI)网络和mRNA半衰期,证明蛋白质在PPI网络中的中心性与其mRNA半衰期密切相关。我们发现相互作用的蛋白质往往表现出相似的半衰期,这在网络中通常被称为 assortative 行为,在生物和社会网络中经常出现。虽然大部分相互作用的蛋白质在mRNA稳定性上显示出显著较低的差异,但一小部分但数量可观的蛋白质对往往表现出比随机预期更高的差异。转录稳定性的较大差异通常涉及那些编码转录因子和酶的蛋白质,这表明在翻译后水平存在反馈联系。我们还注意到,尽管在PPI网络中作为体内中心性代表的必需基因与非必需基因相比高度表达,但它们并不比非必需基因编码更稳定的转录本。我们的结果提供了mRNA稳定性与蛋白质在PPI网络中的中心性之间的直接联系,表明转录后机制对细胞中新生RNA的重要性。