Department of Molecular Biology, Massachusetts General Hospital, Boston, MA.
Department of Genetics, Harvard Medical School, Boston, MA.
J Cell Biol. 2020 Nov 2;219(11). doi: 10.1083/jcb.201910148.
During mitosis, the genome is transformed from a decondensed, transcriptionally active state to a highly condensed, transcriptionally inactive state. Mitotic chromosome reorganization is marked by the general attenuation of transcription on chromosome arms, yet how the cell regulates nuclear and chromatin-associated RNAs after chromosome condensation and nuclear envelope breakdown is unknown. SAF-A/hnRNPU is an abundant nuclear protein with RNA-to-DNA tethering activity, coordinated by two spatially distinct nucleic acid-binding domains. Here we show that RNA is evicted from prophase chromosomes through Aurora-B-dependent phosphorylation of the SAF-A DNA-binding domain; failure to execute this pathway leads to accumulation of SAF-A-RNA complexes on mitotic chromosomes, defects in metaphase chromosome alignment, and elevated rates of chromosome missegregation in anaphase. This work reveals a role for Aurora-B in removing chromatin-associated RNAs during prophase and demonstrates that Aurora-B-dependent relocalization of SAF-A during cell division contributes to the fidelity of chromosome segregation.
在有丝分裂过程中，基因组从解压缩、转录活跃的状态转变为高度浓缩、转录不活跃的状态。有丝分裂染色体的重组以染色体臂上转录的普遍减弱为标志，然而，细胞在染色体浓缩和核膜破裂后如何调节核和染色质相关的 RNA 尚不清楚。SAF-A/hnRNPU 是一种丰富的核蛋白，具有 RNA 到 DNA 的连接活性，由两个空间上不同的核酸结合结构域协调。在这里，我们表明 RNA 通过 Aurora-B 依赖性磷酸化 SAF-A 的 DNA 结合结构域从前期染色体中被逐出；未能执行此途径会导致 SAF-A-RNA 复合物在前中期染色体上积累，中期染色体排列缺陷，并在后期染色体错误分离的速率升高。这项工作揭示了 Aurora-B 在前期去除染色质相关 RNA 的作用，并表明细胞分裂过程中 Aurora-B 依赖性 SAF-A 的重定位有助于染色体分离的保真度。
