School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK.
Randall Division of Cell and Molecular Biophysics, King's College London, Guys Campus, London, SE1 1UL, UK.
Nat Commun. 2017 Nov 30;8(1):1871. doi: 10.1038/s41467-017-02050-w.
Myosin VI (MVI) has been found to be overexpressed in ovarian, breast and prostate cancers. Moreover, it has been shown to play a role in regulating cell proliferation and migration, and to interact with RNA Polymerase II (RNAPII). Here, we find that backfolding of MVI regulates its ability to bind DNA and that a putative transcription co-activator NDP52 relieves the auto-inhibition of MVI to enable DNA binding. Additionally, we show that the MVI-NDP52 complex binds RNAPII, which is critical for transcription, and that depletion of NDP52 or MVI reduces steady-state mRNA levels. Lastly, we demonstrate that MVI directly interacts with nuclear receptors to drive expression of target genes, thereby suggesting a link to cell proliferation and migration. Overall, we suggest MVI may function as an auxiliary motor to drive transcription.
肌球蛋白 VI（MVI）在卵巢癌、乳腺癌和前列腺癌中被发现过度表达。此外，它已被证明在调节细胞增殖和迁移以及与 RNA 聚合酶 II（RNAPII）相互作用方面发挥作用。在这里，我们发现 MVI 的反向折叠调节其与 DNA 结合的能力，并且假定的转录共激活因子 NDP52 解除 MVI 的自动抑制以实现 DNA 结合。此外，我们表明，MVI-NDP52 复合物与 RNAPII 结合，这对转录至关重要，并且 NDP52 或 MVI 的耗竭会降低稳态 mRNA 水平。最后，我们证明 MVI 直接与核受体相互作用以驱动靶基因的表达，从而提示与细胞增殖和迁移有关。总的来说，我们认为 MVI 可能作为辅助马达来驱动转录。
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