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, Chinese Academy of Sciences University of Chinese Academy of Sciences, Shanghai, China.
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
EMBO J. 2019 May 2;38(9). doi: 10.15252/embj.201899910. Epub 2019 Mar 11.
The RNA-binding protein ALYREF plays key roles in nuclear export and also 3'-end processing of polyadenylated mRNAs, but whether such regulation also extends to non-polyadenylated RNAs is unknown. Replication-dependent (RD)-histone mRNAs are not polyadenylated, but instead end in a stem-loop (SL) structure. Here, we demonstrate that ALYREF prevalently binds a region next to the SL on RD-histone mRNAs. SL-binding protein (SLBP) directly interacts with ALYREF and promotes its recruitment. ALYREF promotes histone pre-mRNA 3'-end processing by facilitating U7-snRNP recruitment through physical interaction with the U7-snRNP-specific component Lsm11. Furthermore, ALYREF, together with other components of the TREX complex, enhances histone mRNA export. Moreover, we show that 3'-end processing promotes ALYREF recruitment and histone mRNA export. Together, our results point to an important role of ALYREF in coordinating 3'-end processing and nuclear export of non-polyadenylated mRNAs.
RNA 结合蛋白 ALYREF 在核输出和多聚腺苷酸化 mRNA 的 3'端加工中发挥关键作用，但这种调节是否也扩展到非多聚腺苷酸化的 RNA 尚不清楚。复制依赖性（RD）-组蛋白 mRNA 不进行多聚腺苷酸化，而是在茎环（SL）结构中终止。在这里，我们证明 ALYREF 优先结合 RD-组蛋白 mRNA 上 SL 附近的区域。SL 结合蛋白（SLBP）直接与 ALYREF 相互作用，并促进其募集。ALYREF 通过与 U7-snRNP 特异性成分 Lsm11 的物理相互作用促进 U7-snRNP 的募集，从而促进组蛋白前体 mRNA 的 3'端加工。此外，ALYREF 与 TREX 复合物的其他成分一起增强组蛋白 mRNA 的输出。此外，我们表明 3'端加工促进了 ALYREF 的募集和组蛋白 mRNA 的输出。总之，我们的结果表明 ALYREF 在协调非多聚腺苷酸化 mRNA 的 3'端加工和核输出中起重要作用。
