Microtubule-dependent endosomal transport is crucial for polar growth, ensuring the precise distribution of cellular cargos such as proteins and mRNAs. However, the molecular mechanism linking mRNAs to the endosomal surface remains poorly understood. Here, we present a structural analysis of the key RNA-binding protein Rrm4 from Ustilago maydis . Our findings reveal a different type of MademoiseLLE domain (MLLE) featuring a seven-helical bundle that provides a distinct binding interface. A comparative analysis with the canonical MademoiseLLE domain of the poly(A)-binding protein Pab1 disclosed unique characteristics of both domains. Deciphering the MLLE binding code enabled prediction and verification of previously unknown Rrm4 interactors containing short linear motifs. Importantly, we demonstrated that the human MLLE domains, such as those of PABPC1 and UBR5, employed a similar principle to distinguish among interaction partners. Thus, our study provides detailed mechanistic insights into how structural variations in the widely distributed MLLE domain facilitate mRNA attachment during endosomal transport.

中文翻译：

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破译内体 mRNA 运输过程中的 RNA 结合蛋白网络


微管依赖性内体转运对于极性生长至关重要，可确保蛋白质和 mRNA 等细胞货物的精确分布。然而，将 mRNA 连接到内体表面的分子机制仍然知之甚少。在这里，我们介绍了来自 Ustilago maydis 的关键 RNA 结合蛋白 Rrm4 的结构分析。我们的研究结果揭示了一种不同类型的 MademoiseLLE 结构域 （MLLE），具有提供独特结合界面的七螺旋束。与 poly （A） 结合蛋白 Pab1 的经典 MademoiseLLE 结构域的比较分析揭示了两个结构域的独特特征。破译 MLLE 结合代码可以预测和验证以前未知的包含短线性基序的 Rrm4 交互子。重要的是，我们证明了人类 MLLE 结构域，例如 PABPC1 和 UBR5 的结构域，采用类似的原理来区分交互伙伴。因此，我们的研究提供了详细的机制见解，了解广泛分布的 MLLE 结构域中的结构变化如何促进内体运输过程中的 mRNA 附着。