In-silico DFs import results for permutations on DFs interactions, tested for Xrn1D208A mutation.

The Xrn1D208A mutation forces the factors that directly or indirectly interact with Xrn1D208A to stay in the cytoplasm and not import into the nucleus. Using this mutation, we initiated our model with various permutations on decay factors interactions, executed the model for each such permutation to predict the import status of each decay factor and compared it to our in-vivo observations.There are 4096 (212) possible permutations for the interactions of the decay factors. We chose to execute 11 permutations (columns 1–11), where 3 of them (column 4, 6, 7) were verified by the model to match the experimental findings. Two of these options are presented graphically in Figure S2 in File S1. The executions in column 1, 2 and 3 includes our initial conjectures and do not match the experimental findings. In the executions presented in columns 4–11, the direct interactions between Pat1 and Edc3, and Lsm1-7 were eliminated, since our experiments argued against them (see Figure 4). The “Model Initiation” rows represent the model initiations with various possible decay factors interactions and “Model Predictions” rows represent the model outcomes of decay factors import status. The (*) sign in the “Model Predictions” rows highlights the in-silico outcomes that contradict our in-vivo observations presented in Figure 4 and Table 1 (i.e., for Xrn1D208A we observed that Xrn1 = no import, Dcp1 = no import, Dcp2 = no import, Pat1 = no import, Lsm1 = import and Edc3 = import).In-silico DFs import results for permutations on DFs interactions, tested for Xrn1D208A mutation.

Xrn1D208A突变可使与其直接或间接相互作用的因子滞留于细胞质内，无法向细胞核转运。基于该突变体，我们针对降解因子间的相互作用构建了多种排列组合模型，对每一种组合执行模型推演以预测各降解因子的核转运状态，并将预测结果与体内观测结果进行比对。降解因子的相互作用共存在4096（2¹²）种可能的排列组合。我们选取了其中11种组合（第1至11列）开展推演，其中3种组合（第4、6、7列）经模型验证与实验发现相符。其中两种组合已在补充材料S1中的图S2中以图形形式展示。第1、2、3列的推演基于我们最初的推测，与实验结果不符。在第4至11列的推演中，我们排除了Pat1与Edc3以及Lsm1-7之间的直接相互作用，因为实验结果不支持这类相互作用（详见图4）。"模型初始化"行代表基于各类可能的降解因子相互作用所构建的模型初始化方案，"模型预测"行则代表各模型对降解因子核转运状态的推演结果。"模型预测"行中的星号（*）标记了与图4及表1中体内观测结果相悖的计算机模拟推演结果：针对Xrn1D208A突变，我们观测到的结果为Xrn1无法入核、Dcp1无法入核、Dcp2无法入核、Pat1无法入核、Lsm1可入核且Edc3可入核。本数据集为针对Xrn1D208A突变，基于降解因子相互作用排列组合得到的计算机模拟降解因子转运结果。