Division of Integrated Life Sciences, Graduate School of Biostudies, Kyoto University, Kyoto, Kyoto, 606-8502, Japan.
Division of Gene Expression Mechanism, Center for Medical Science, Fujita Health University, Toyoake, Aichi, 470-1192, Japan.
Nat Commun. 2024 Jan 15;15(1):455. doi: 10.1038/s41467-023-44217-8.
mRNA export is an essential pathway for the regulation of gene expression. In humans, closely related RNA helicases, UAP56 and URH49, shape selective mRNA export pathways through the formation of distinct complexes, known as apo-TREX and apo-AREX complexes, and their subsequent remodeling into similar ATP-bound complexes. Therefore, defining the unidentified components of the apo-AREX complex and elucidating the molecular mechanisms underlying the formation of distinct apo-complexes is key to understanding their functional divergence. In this study, we identify additional apo-AREX components physically and functionally associated with URH49. Furthermore, by comparing the structures of UAP56 and URH49 and performing an integrated analysis of their chimeric mutants, we exhibit unique structural features that would contribute to the formation of their respective complexes. This study provides insights into the specific structural and functional diversification of these two helicases that diverged from the common ancestral gene Sub2.
mRNA 输出是基因表达调控的一个重要途径。在人类中，密切相关的 RNA 解旋酶 UAP56 和 URH49 通过形成不同的复合物，即无帽 TREX 和无帽 AREX 复合物，并进一步重塑为类似的 ATP 结合复合物，来塑造选择性的 mRNA 输出途径。因此，确定无帽 AREX 复合物中未被识别的成分，并阐明形成不同无帽复合物的分子机制，是理解它们功能分化的关键。在这项研究中，我们从物理和功能上鉴定了与 URH49 相关的其他无帽 AREX 成分。此外，通过比较 UAP56 和 URH49 的结构，并对它们的嵌合体突变体进行综合分析，我们展示了独特的结构特征，这些特征将有助于形成它们各自的复合物。这项研究为这两个从共同祖先基因 Sub2 分化而来的解旋酶的特定结构和功能多样化提供了深入了解。
