AURKB-driven dissolution of CIZ1–RNA assemblies from the inactive X chromosome in mitosis

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Abstract
Cip1-interacting zinc-finger protein 1 (CIZ1) interacts with Xist lncRNA to form large RNA–protein assemblies at the inactive X-chromosome (Xi) in female mammalian nuclei, plus smaller assemblies in both sexes. CIZ1 assemblies influence underlying chromatin, and their disruption alters the expression of autosomal and X-linked gene clusters. Here, we explore the regulated dissolution of CIZ1–Xi assemblies during mitosis and show that, like Xist, CIZ1 is released in prometaphase under the regulation of Aurora Kinase B (AURKB). The part of human/mouse CIZ1 comprising 179/181 C-terminal amino acids encodes a matrin-3 domain that facilitates dimerization to form a compact folded core with disordered C-terminal extensions. Mass spectrometry revealed 56 high-confidence interacting partners of the C-terminal fragment, predominantly chromatin, nuclear matrix, and RNA-binding proteins. Phosphomimetic mutation of three conserved AURKB sites in the C-terminal extensions released CIZ1 from its nuclear anchor points, but did not affect its interaction with chromatin or nuclear matrix proteins. In contrast, the same mutations, or deletion of the C-terminal extensions, abolished interaction with RNAs, including Xist. Together, the data suggest CIZ1 is a regulatable component of the protein–RNA assemblies that preserve epigenetic stability across the nucleus, and that AURKB drives their dissolution in mitosis via dissociation of CIZ1 from RNA.
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Funding Information
  • Engineering and Physical Sciences Research Council (EP/K039660/1)
  • Engineering and Physical Sciences Research Council (EP/M028127/1)
  • BBSRC (BB/T007222/1)
  • Royal Society Leverhulme Trust (SRF\R1\191028)
  • Wellcome Trust (224665)
  • Medical Research Council (MR/V029088/1)

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