Animal Physiology Group, Department of Biology, University of Kaiserslautern, Kaiserslautern, Germany.
Synaptopathies and Autoantibodies, Institut NeuroMyoGène INSERM U1217/ CNRS, UMR 5310, Faculty of Medicine, University Jean Monnet, Saint-Étienne, France.
J Neurochem. 2019 Jun;149(5):582-604. doi: 10.1111/jnc.14664. Epub 2019 Feb 14.
Transcription, translation, and turnover of transcripts and proteins are essential for cellular function. The contribution of those factors to protein levels is under debate, as transcript levels and cognate protein levels do not necessarily correlate due to regulation of translation and protein turnover. Here we propose neuronal polarity as a third factor that is particularly evident in the CNS, leading to considerable distances between somata and axon terminals. Consequently, transcript levels may negatively correlate with cognate protein levels in CNS regions, i.e., transcript and protein levels behave reciprocally. To test this hypothesis, we performed an integrative inter-omics study and analyzed three interconnected rat auditory brainstem regions (cochlear nuclear complex, CN; superior olivary complex, SOC; inferior colliculus, IC) and the rest of the brain as a reference. We obtained transcript and protein sets in these regions of interest (ROIs) by DNA microarrays and label-free mass spectrometry, and performed principal component and correlation analyses. We found 508 transcript|protein pairs and detected poor to moderate transcript|protein correlation in all ROIs, as evidenced by coefficients of determination from 0.34 to 0.54. We identified 57-80 negatively correlating gene products in the ROIs and intensively analyzed four of them for which the correlation was poorest. Three cognate proteins (Slc6a11, Syngr1, Tppp) were synaptic and hence candidates for a negative correlation because of protein transport into axon terminals. Thus, we systematically analyzed the negatively correlating gene products. Gene ontology analyses revealed overrepresented transport/synapse-related proteins, supporting our hypothesis. We present 30 synapse/transport-related proteins with poor transcript|protein correlation. In conclusion, our analyses support that protein transport in polar cells is a third factor that influences the protein level and, thereby, the transcript|protein correlation. OPEN SCIENCE BADGES: This article has received a badge for Open Materials and Open Data because it provided all relevant information to reproduce the study in the manuscript and because it made the data publicly available. The data can be accessed at https://osf.io/ha28n/. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
转录、翻译和转录本及蛋白质的周转是细胞功能所必需的。由于翻译和蛋白质周转的调控，转录本水平和同源蛋白水平不一定相关，因此这些因素对蛋白质水平的贡献仍存在争议。在这里，我们提出神经元极性作为第三个因素，在中枢神经系统中尤为明显，导致胞体和轴突末端之间存在相当大的距离。因此，在中枢神经系统区域，转录本水平可能与同源蛋白水平呈负相关，即转录本和蛋白质水平互为反相关。为了验证这一假设，我们进行了一项综合的组学研究，分析了三个相互连接的大鼠听觉脑干区域（耳蜗核复合体、CN；上橄榄复合体、SOC；下丘，IC）和大脑的其余部分作为参考。我们通过 DNA 微阵列和无标记质谱获得了这些感兴趣区域（ROI）的转录本和蛋白质组，并进行了主成分和相关性分析。我们发现了 508 个转录本|蛋白对，并在所有 ROI 中检测到较差到中等的转录本|蛋白相关性，这从决定系数 0.34 到 0.54 中可以得到证明。我们在 ROI 中鉴定了 57-80 个负相关的基因产物，并对其中四个相关性最差的基因产物进行了深入分析。三个同源蛋白（Slc6a11、Syngr1、Tppp）是突触蛋白，因此由于蛋白质被运输到轴突末端，它们是负相关的候选者。因此，我们系统地分析了负相关的基因产物。基因本体分析显示，过表达的运输/突触相关蛋白支持我们的假设。我们提出了 30 个与突触/运输相关的蛋白，其转录本|蛋白相关性较差。总之，我们的分析支持蛋白质在极性细胞中的运输是影响蛋白质水平的第三个因素，从而影响转录本|蛋白相关性。开放科学徽章：本文获得了“开放材料”和“开放数据”徽章，因为它提供了重现文章中研究的所有相关信息，并且因为它使数据公开可用。数据可在 https://osf.io/ha28n/ 访问。本文完整的开放科学披露表格可在文章末尾找到。有关开放实践徽章的更多信息可以在 https://cos.io/our-services/open-science-badges/ 找到。
