NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction
作者单位：Shanghai Institute of Biochemistry and Cell Biology University of Chinese Academy of Sciences
会议名称：《中国生物化学与分子生物学会2019年全国学术会议暨学会...》
会议日期：2019年
学科分类：0710[理学-生物学] 07[理学] 071007[理学-遗传学]
关 键 词：NRDE2 the nuclear exosome MTR4 recruitment mRNA export
摘 要：The exosome functions in the degradation of diverse RNA species, yet how it is negatively regulated remains largely unknown. Here, we show that NRDE2 forms a 1:1 complex with MTR4, a nuclear exosome cofactor critical for exosome recruitment, via a conserved MTR4-interacting domain(MID). Unexpectedly, NRDE2 mainly localizes in nuclear speckles, where it inhibits MTR4 recruitment and RNA degradation, and thereby ensures efficient mRNA nuclear export. Structural and biochemical data revealed that NRDE2 interacts with MTR4’s key residues, locks MTR4 in a closed conformation, and inhibits MTR4 interaction with the exosome as well as proteins important for MTR4 recruitment, such as the cap-binding complex(CBC) and ZFC3 H1. Functionally, MID deletion results in the loss of self-renewal of mouse embryonic stem cells. Together, our data pinpoint NRDE2 as a nuclear exosome negative regulator that ensures mRNA stability and nuclear export.