Yu Nam-Kyung, McClatchy Daniel B, Diedrich Jolene K, Romero Sarah, Choi Jun-Hyeok, Martínez-Bartolomé Salvador, Delahunty Claire M, Muotri Alysson R, Yates John R
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, School of Medicine, University of California, San Diego, San Diego, CA 92037, USA.
iScience. 2021 Oct 23;24(11):103321. doi: 10.1016/j.isci.2021.103321. eCollection 2021 Nov 19.
A single protein can be multifaceted depending on the cellular contexts and interacting molecules. LIN28A is an RNA-binding protein that governs developmental timing, cellular proliferation, differentiation, stem cell pluripotency, and metabolism. In addition to its best-known roles in microRNA biogenesis, diverse molecular roles have been recognized. In the nervous system, LIN28A is known to play critical roles in proliferation and differentiation of neural progenitor cells (NPCs). We profiled the endogenous LIN28A-interacting proteins in NPCs differentiated from human induced pluripotent stem (iPS) cells using immunoprecipitation and liquid chromatography-tandem mass spectrometry. We identified over 500 LIN28A-interacting proteins, including 156 RNA-independent interactors. Functions of these proteins span a wide range of gene regulatory processes. Prompted by the interactome data, we revealed that LIN28A may impact the subcellular distribution of its interactors and stress granule formation upon oxidative stress. Overall, our analysis opens multiple avenues for elaborating molecular roles and characteristics of LIN28A.
单一蛋白质可能因细胞环境和相互作用分子而具有多面性。LIN28A是一种RNA结合蛋白，它调控发育时间、细胞增殖、分化、干细胞多能性和代谢。除了在微小RNA生物合成中最广为人知的作用外，其多样的分子作用也已被认识到。在神经系统中，已知LIN28A在神经祖细胞（NPC）的增殖和分化中起关键作用。我们使用免疫沉淀和液相色谱-串联质谱分析了从人诱导多能干细胞（iPS）分化而来的NPC中内源性LIN28A相互作用蛋白。我们鉴定出500多种LIN28A相互作用蛋白，包括156种不依赖RNA的相互作用蛋白。这些蛋白的功能涵盖广泛的基因调控过程。受相互作用组数据的启发，我们发现LIN28A可能影响其相互作用蛋白的亚细胞分布以及氧化应激时应激颗粒的形成。总体而言，我们的分析为阐明LIN28A的分子作用和特性开辟了多条途径。
