Cell division requires RNA eviction from condensing chromosomes

• Published in: The Journal of cell biology Vol. 219; no. 11
• Main Authors: Sharp, Judith A, Perea-Resa, Carlos, Wang, Wei, Blower, Michael D
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 02.11.2020
• Subjects: Aurora Kinase B - genetics; Aurora Kinase B - metabolism; Cell Nucleus - genetics; Chromatin - chemistry; Chromatin - genetics; Chromatin or Epigenetics; Chromosomes, Human - chemistry; Chromosomes, Human - genetics; HEK293 Cells; Heterogeneous-Nuclear Ribonucleoprotein U - genetics; Heterogeneous-Nuclear Ribonucleoprotein U - metabolism; Humans; Mitosis; Phosphorylation; RNA - genetics; RNA - metabolism
• ISSN: 0021-9525; 1540-8140
• 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.