Fan Jing, Kuai Bin, Wu Guifen, Wu Xudong, Chi Binkai, Wang Lantian, Wang Ke, Shi Zhubing, Zhang Heng, Chen She, He Zhisong, Wang Siyuan, Zhou Zhaocai, Li Guohui, Cheng Hong
State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
EMBO J. 2017 Oct 2;36(19):2870-2886. doi: 10.15252/embj.201696139. Epub 2017 Aug 11.
The exosome is a key RNA machine that functions in the degradation of unwanted RNAs. Here, we found that significant fractions of precursors and mature forms of mRNAs and long noncoding RNAs are degraded by the nuclear exosome in normal human cells. Exosome-mediated degradation of these RNAs requires its cofactor hMTR4. Significantly, hMTR4 plays a key role in specifically recruiting the exosome to its targets. Furthermore, we provide several lines of evidence indicating that hMTR4 executes this role by directly competing with the mRNA export adaptor ALYREF for associating with ARS2, a component of the cap-binding complex (CBC), and this competition is critical for determining whether an RNA is degraded or exported to the cytoplasm. Together, our results indicate that the competition between hMTR4 and ALYREF determines exosome recruitment and functions in creating balanced nuclear RNA pools for degradation and export.
外泌体是一种关键的RNA机器，其功能是降解不需要的RNA。在此，我们发现，在正常人类细胞中，核外泌体会降解相当一部分mRNA和长链非编码RNA的前体及成熟形式。外泌体介导的这些RNA的降解需要其辅助因子hMTR4。值得注意的是，hMTR4在将外泌体特异性招募到其靶标方面起着关键作用。此外，我们提供了几条证据表明，hMTR4通过直接与mRNA输出衔接蛋白ALYREF竞争，以与帽结合复合物（CBC）的一个组分ARS2结合来执行这一作用，而这种竞争对于确定RNA是被降解还是输出到细胞质至关重要。总之，我们的结果表明，hMTR4与ALYREF之间的竞争决定了外泌体的招募，并在创建用于降解和输出的平衡核RNA库中发挥作用。
