ALBA protein complex reads genic R-loops to maintain genome stability in Arabidopsis

First author: Wei Yuan; Affiliations: Peking University (北京大学): Beijing, China

Corresponding author: Weiqiang Qian

The R-loop, composed of a DNA-RNA hybrid and the displaced single-stranded DNA, regulates diverse cellular processes. However, how cellular R-loops are recognized remains poorly understood. Here, we report the discovery of the evolutionally conserved ALBA proteins (AtALBA1 and AtALBA2) functioning as the genic R-loop readers in Arabidopsis. While AtALBA1 binds to the DNA-RNA hybrid, AtALBA2 associates with single-stranded DNA in the R-loops in vitro. In vivo, these two proteins interact and colocalize in the nucleus, where they preferentially bind to genic regions with active epigenetic marks in an R-loop–dependent manner. Depletion of AtALBA1 or AtALBA2 results in hypersensitivity of plants to DNA damaging agents. The formation of DNA breaks in alba mutants originates from unprotected R-loops. Our results reveal that the AtALBA1 and AtALBA2 protein complex is the genic R-loop reader crucial for genome stability in Arabidopsis.

R环由一条DNA-RNA杂合链以及一条非模版DNA单链构成的环状结构，该结构调控许多的细胞学进程。然而，细胞中R环的识别机制还不清楚。本文，作者发现了一个演化上比较保守的蛋白ALBA能够“读取”R环，拟南芥中有两个ALBA蛋白，分别是ALBA1和ALBA2。体外试验条件下，当ALBA1蛋白结合到DNA-RNA杂合链上时，AtALBA2与R环剩下的一条DNA单链联合在一起。体内试验中，这两个蛋白能够相互作用，并且共定位于细胞核中，通过R环依赖型方式优先结合到具有活性表观标记的基因组区域。AtALBA1或者AtALBA2的功能缺失能够导致植物对于DNA损伤事件的超敏感。在alba突变体中，DNA断裂的形成大多位于没有R环的基因组区域。本文的结果揭示了拟南芥中AtALBA1和AtALBA2蛋白复合体作用于R环的“读取”，对于基因组的稳定至关重要。

通讯：钱伟强（http://www.pepge.pku.edu.cn/index.php?s=/Index/team/cid/15/id/657.html）

研究方向：1、植物基因组DNA主动去甲基化的分子机制和生物学功能；2、植物基因沉默的表观遗传学机制；3、植物非编码RNA的功能鉴定。

doi: 10.1126/sciadv.aav9040

Journal: Science Advance

Published date: May 15, 2019