The MYCN oncoprotein broadly binds active promoters in a heterodimer with its partner protein MAX. MYCN also interacts with the nuclear exosome, a 3'-5' exoribonuclease complex, suggesting a function in RNA metabolism. Here we show that MYCN forms stable high molecular weight complexes with the exosome and multiple RNA-binding proteins. In cells, MYCN binds to thousands of intronic RNAs; recombinant MYCN directly binds RNA via a short, highly conserved sequence termed MYCBoxI. Perturbing exosome function results in global re-localization of MYCN from promoters to intronic RNAs. At promoters, MYCN is then replaced by the MNT(MXD6) repressor protein, which inhibits MYCN-dependent transcription. MYCN promotes the degradation of its bound introns via the nuclear exosome targeting (NEXT) complex. Our data demonstrate that MYCN is an RNA-binding protein that regulates nascent transcript turnover and show that competition between its RNA- and DNA-bound states links the dynamics of the MYCN/MAX/MXD network to mRNA processing.

中文翻译：

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MYCN 与 RNA 的直接结合介导从 RNA 加工到转录控制的反馈

MYCN 癌蛋白与其伴侣蛋白 MAX 广泛结合异二聚体中的活性启动子。MYCN 还与核外泌体（一种 3'-5' 外核糖核酸酶复合物）相互作用，表明其在 RNA 代谢中具有功能。在这里，我们证明 MYCN 与外泌体和多种 RNA 结合蛋白形成稳定的高分子量复合物。在细胞中，MYCN 与数千个内含子 RNA 结合；重组 MYCN 通过称为 MYCBoxI 的短且高度保守的序列直接结合 RNA。干扰外泌体功能会导致 MYCN 从启动子到内含子 RNA 的整体重新定位。在启动子处，MYCN 随后被 MNT(MXD6) 阻遏蛋白取代，从而抑制 MYCN 依赖性转录。MYCN 通过核外泌体靶向 (NEXT) 复合物促进其结合内含子的降解。