Arva Akshaya, Kasu Yasar Arfat T, Duncan Jennifer, Alkhatatbeh Mosleh A, Brower Christopher S
Department of Biology, Texas Woman's University, Denton, TX 76204.
Department of Biology, Texas Woman's University, Denton, TX 76204
Proc Natl Acad Sci U S A. 2021 Jan 5;118(1). doi: 10.1073/pnas.2015887118. Epub 2020 Dec 21.
The Ligand of Ate1 (Liat1) is a protein of unknown function that was originally discovered through its interaction with arginyl-tRNA protein transferase 1 (Ate1), a component of the Arg/N-degron pathway of protein degradation. Here, we characterized the functional domains of mouse Liat1 and found that its N-terminal half comprises an intrinsically disordered region (IDR) that facilitates its liquid-liquid phase separation (LLPS) in the nucleolus. Using bimolecular fluorescence complementation and immunocytochemistry, we found that Liat1 is targeted to the nucleolus by a low-complexity poly-K region within its IDR. We also found that the lysyl-hydroxylase activity of Jumonji Domain Containing 6 (Jmjd6) modifies Liat1, in a manner that requires the Liat1 poly-K region, and inhibits its nucleolar targeting and potential functions. In sum, this study reveals that Liat1 participates in nucleolar LLPS regulated by Jmjd6.
Ate1的配体（Liat1）是一种功能未知的蛋白质，最初是通过其与精氨酰-tRNA蛋白转移酶1（Ate1）的相互作用而被发现的，Ate1是蛋白质降解的Arg/N-降解途径的一个组成部分。在此，我们对小鼠Liat1的功能结构域进行了表征，发现其N端的一半包含一个内在无序区域（IDR），该区域促进其在核仁中的液-液相分离（LLPS）。使用双分子荧光互补和免疫细胞化学方法，我们发现Liat1通过其IDR内的一个低复杂性多聚K区域靶向核仁。我们还发现，含Jumonji结构域6（Jmjd6）的赖氨酰羟化酶活性以一种需要Liat1多聚K区域的方式修饰Liat1，并抑制其核仁靶向和潜在功能。总之，这项研究揭示了Liat1参与了由Jmjd6调节的核仁LLPS。
