RNA颗粒使用Annexin A11蛋白作为分子拴绳搭便车到溶酶体上进行长距离运输，这一成果由美国霍华德休斯医学研究所Jennifer Lippincott-Schwartz组取得。该项研究成果发表在2019年9月19日出版的《细胞》上。
研究人员发现一种RNA转运机制，其中RNA颗粒“搭便车”在移动的溶酶体上。体外生物物理模拟、活细胞显微镜和无偏倚的邻近标记蛋白质组学揭示了膜联蛋白A11（ANXA11），一种RNA颗粒相关的磷酸肌醇结合蛋白，作为RNA颗粒和溶酶体之间的分子拴绳。ANXA11具有N-末端低复杂性结构域，促进其相分离成无膜RNA颗粒，以及C-末端膜结合结构域，使其能够与溶酶体相互作用。RNA颗粒转运需要ANXA11，并且ANXA11中的肌萎缩侧索硬化（ALS）相关突变通过破坏它们与溶酶体的相互作用而损害RNA颗粒转运。因此，ANXA11通过将RNA颗粒束缚到活跃转运的溶酶体来介导神经元RNA转运，从而执行在ALS中被破坏的关键细胞功能。
据了解，长距离RNA转运使得能够在远离细胞核的代谢活性位点处进行局部蛋白质合成。这个过程确保蛋白质的恰当空间定位，对极化细胞如神经元至关重要。
附：英文原文
Title: RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether
Author: Ya-Cheng Liao, Michael S. Fernandopulle, Guozhen Wang, Heejun Choi, Ling Hao, Catherine M. Drerup, Rajan Patel, Seema Qamar, Jonathon Nixon-Abell, Yi Shen, William Meadows, Michele Vendruscolo, Tuomas P.J. Knowles, Matthew Nelson, Magdalena A. Czekalska, Greta Musteikyte, Mariam A. Gachechiladze, Christina A. Stephens, H. Amalia Pasolli, Lucy R. Forrest, Peter St George-Hyslop, Jennifer Lippincott-Schwartz, Michael E. Ward
Issue&Volume: Volume 179 Issue 1
Abstract: Long-distance RNA transport enables local protein synthesis at metabolically-active sites distant from the nucleus. This process ensures an appropriate spatial organization of proteins, vital to polarized cells such as neurons. Here, we present a mechanism for RNA transport in which RNA granules “hitchhike” on moving lysosomes. In vitro biophysical modeling, live-cell microscopy, and unbiased proximity labeling proteomics reveal that annexin A11 (ANXA11), an RNA granule-associated phosphoinositide-binding protein, acts as a molecular tether between RNA granules and lysosomes. ANXA11 possesses an N-terminal low complexity domain, facilitating its phase separation into membraneless RNA granules, and a C-terminal membrane binding domain, enabling interactions with lysosomes. RNA granule transport requires ANXA11, and amyotrophic lateral sclerosis (ALS)-associated mutations in ANXA11 impair RNA granule transport by disrupting their interactions with lysosomes. Thus, ANXA11 mediates neuronal RNA transport by tethering RNA granules to actively-transported lysosomes, performing a critical cellular function that is disrupted in ALS.
DOI: 10.1016/j.cell.2019.08.050
Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30969-9