Eukaryotic superfamily (SF) 1 helicases have been implicated in various aspects of RNA metabolism, including transcription, processing, translation, and degradation. Nevertheless, until now, most human SF1 helicases remain poorly understood. Here, we have functionally and biochemically characterized the role of a putative SF1 helicase termed "helicase with zinc-finger," or HELZ. We discovered that HELZ associates with various mRNA decay factors, including components of the carbon catabolite repressor 4-negative on TATA box (CCR4-NOT) deadenylase complex in human and Drosophila melanogaster cells. The interaction between HELZ and the CCR4-NOT complex is direct and mediated by extended low-complexity regions in the C-terminal part of the protein. We further reveal that HELZ requires the deadenylase complex to mediate translational repression and decapping-dependent mRNA decay. Finally, transcriptome-wide analysis of Helz-null cells suggests that HELZ has a role in the regulation of the expression of genes associated with the development of the nervous system.

中文翻译：

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HELZ与CCR4-NOT直接相互作用，并导致结合的mRNA衰减。

真核超家族（SF）1解旋酶已牵涉到RNA代谢的各个方面，包括转录，加工，翻译和降解。尽管如此，直到现在，大多数人类SF1解旋酶仍知之甚少。在这里，我们已经在功能上和生化特征上描述了一种假定的SF1解旋酶的作用，称为“带有锌指的解旋酶”或HELZ。我们发现HELZ与各种mRNA衰减因子相关，包括人类和果蝇中TATA框（CCR4-NOT）腺苷酸酶复合物上的碳分解代谢物阻遏物4阴性的成分。细胞。HELZ与CCR4-NOT复合物之间的相互作用是直接的，并由蛋白质C端部分中扩展的低复杂度区域介导。我们进一步揭示，HELZ需要去烯基化酶复合物来介导翻译抑制和去盖依赖性的mRNA衰减。最后，全基因组范围的分析HELZ -null细胞表明，HELZ具有与神经系统的发育相关的基因表达的调节作用。