A Synthetic Biology Approach Identifies the Mammalian UPR RNA Ligase RtcB

作者：Lu Yanyan; Liang Feng Xia; Wang Xiaozhong^*

来源：Molecular Cell, 2014, 55(5): 758-770.

DOI：10.1016/j.molcel.2014.06.032

Signaling in the ancestral branch of the unfolded protein response (UPR) is initiated by unconventional splicing of HAC1/XBP1 mRNA during endoplasmic reticulum (ER) stress. In mammals, IRE1a has been known to cleave the XBP1 intron. However, the enzyme responsible for ligation of two XBP1 exons remains unknown. Using an XBP1 splicing-based synthetic circuit, we identify RtcB as the primary UPR RNA ligase. In RtcB knockout cells, XBP1 mRNA splicing is defective during ER stress. Genetic rescue and in vitro splicing show that the RNA ligase activity of RtcB is directly required for the splicing of XBP1 mRNA. Taken together, these data demonstrate that RtcB is the long-sought RNA ligase that catalyzes unconventional RNA splicing during the mammalian UPR.

• 出版日期2014-9-4
• 单位西北大学