Messenger RNAs (mRNAs) are at the center of the central dogma of molecular biology. In eukaryotic cells, these long ribonucleic acid polymers do not exist as naked transcripts; rather, they associate with mRNA-binding proteins to form messenger ribonucleoprotein (mRNP) complexes. Recently, global proteomic and transcriptomic studies have provided comprehensive inventories of mRNP components. However, knowledge of the molecular features of distinct mRNP populations has remained elusive. We purified endogenous nuclear mRNPs from Saccharomyces cerevisiae by harnessing the mRNP biogenesis factors THO and Sub2 in biochemical procedures optimized to preserve the integrity of these transient ribonucleoprotein assemblies. We found that these mRNPs are compact particles that contain multiple copies of Yra1, an essential protein with RNA-annealing properties. To investigate their molecular and architectural organization, we used a combination of proteomics, RNA sequencing, cryo-electron microscopy, cross-linking mass spectrometry, structural models, and biochemical assays. Our findings indicate that yeast nuclear mRNPs are packaged around an intricate network of interconnected proteins capable of promoting RNA–RNA interactions via their positively charged intrinsically disordered regions. The evolutionary conservation of the major mRNA-packaging factor (yeast Yra1 and Aly/REF in metazoans) points toward a general paradigm governing nuclear mRNP packaging.

中文翻译：

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核 mRNA 是紧凑的颗粒，包裹着促进 RNA-RNA 相互作用的蛋白质网络

信使 RNA (mRNA) 是分子生物学中心法则的核心。在真核细胞中，这些长核糖核酸聚合物并不以裸露的转录本形式存在。相反，它们与 mRNA 结合蛋白结合形成信使核糖核蛋白 (mRNP) 复合物。最近，全球蛋白质组学和转录组学研究提供了 mRNP 成分的全面清单。然而，对不同 mRNP 群体的分子特征的了解仍然难以捉摸。我们通过在优化的生化程序中利用 mRNP 生物合成因子 THO 和 Sub2，从酿酒酵母中纯化内源性核 mRNP ，以保持这些瞬时核糖核蛋白组装体的完整性。我们发现这些 mRNP 是包含多个 Yra1 拷贝的紧凑颗粒，Yra1 是一种具有 RNA 退火特性的必需蛋白质。为了研究它们的分子和结构组织，我们结合使用了蛋白质组学、RNA 测序、冷冻电子显微镜、交联质谱、结构模型和生化测定。我们的研究结果表明，酵母核 mRNA 包装在一个复杂的相互连接的蛋白质网络周围，能够通过其带正电的内在无序区域促进 RNA-RNA 相互作用。主要 mRNA 包装因子（后生动物中的酵母 Yra1 和 Aly/REF）的进化保守性指向了控制核 mRNA 包装的通用范式。