当前位置:科学网首页 > 小柯机器人 >详情
RNA颗粒利用溶酶体“搭便车”
作者:小柯机器人 发布时间:2019/9/20 16:35:15

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

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/