Principles of self-organization in biological pathways: a hypothesis on the autogenous association of alpha-synuclein.
Principles of self-organization in biological pathways: a hypothesis on the autogenous association of alpha-synuclein.
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DOI：
10.1093/nar/gkt794
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发表时间：
2013-12
影响因子：
14.9
通讯作者：
Tartaglia GG
中科院分区：
文献类型：
--
作者：
Zanzoni A;Marchese D;Agostini F;Bolognesi B;Cirillo D;Botta-Orfila M;Livi CM;Rodriguez-Mulero S;Tartaglia GG
先前的证据表明许多蛋白质能够与同源 mRNA 相互作用。这些自体关联代表了在翻译水平上控制基因表达的重要调节机制。我们使用 catRAPID 方法预测蛋白质与 RNA 结合的倾向，研究了人类蛋白质组中自体关联的发生。我们的算法正确识别了众所周知的案例中的结合位点，例如胸苷酸合酶、肿瘤抑制因子 P53、突触结合蛋白-1、富含丝氨酸/精氨酸的剪接因子 2、热休克 70 kDa、核糖核酸颗粒特异性 U1A 和核糖体蛋白 S13。此外，我们发现其他几种蛋白质能够与其自身的 mRNA 结合。对生物途径的大规模分析表明，易于聚集和结构无序的蛋白质与同源 RNA 相互作用的倾向最高。这些发现得到了 TAR DNA 结合蛋白 43 和脆性 X 智力迟钝蛋白等淀粉样蛋白生成蛋白的实验证据的证实。在淀粉样蛋白中，我们预测帕金森病相关的 α-突触核蛋白很容易与同源转录本相互作用，这表明其功能和功能障碍中存在 RNA 依赖性因子。事实上，由于聚集本质上是浓度依赖性的，因此自体相互作用可能在控制蛋白质稳态中发挥至关重要的作用。
Previous evidence indicates that a number of proteins are able to interact with cognate mRNAs. These autogenous associations represent important regulatory mechanisms that control gene expression at the translational level. Using the catRAPID approach to predict the propensity of proteins to bind to RNA, we investigated the occurrence of autogenous associations in the human proteome. Our algorithm correctly identified binding sites in well-known cases such as thymidylate synthase, tumor suppressor P53, synaptotagmin-1, serine/ariginine-rich splicing factor 2, heat shock 70 kDa, ribonucleic particle-specific U1A and ribosomal protein S13. In addition, we found that several other proteins are able to bind to their own mRNAs. A large-scale analysis of biological pathways revealed that aggregation-prone and structurally disordered proteins have the highest propensity to interact with cognate RNAs. These findings are substantiated by experimental evidence on amyloidogenic proteins such as TAR DNA-binding protein 43 and fragile X mental retardation protein. Among the amyloidogenic proteins, we predicted that Parkinson’s disease-related α-synuclein is highly prone to interact with cognate transcripts, which suggests the existence of RNA-dependent factors in its function and dysfunction. Indeed, as aggregation is intrinsically concentration dependent, it is possible that autogenous interactions play a crucial role in controlling protein homeostasis.
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影响因子：
64.5
作者：
Cooper TA;Wan L;Dreyfuss G
通讯作者：
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影响因子：
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Agostini F;Cirillo D;Bolognesi B;Tartaglia GG
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Tartaglia GG
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