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bioRxiv · 10.1101/2025.09.17.676856

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

Byrom, L.·Turvey, G. L.·Dowle, A. A.·Thomas, M.·Shiridkar, N.·Green, B.·Brown, M.·Ball, C.·Chapman, K. E.·Guglielmi, E.·Dickson, W.·Noon, E.·Sofi, S.·Ainscough, J. F.-X.·Antson, A. A.·Coverley, D.
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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. BulletsThe data show regulated dissolution of RNA-protein assemblies involved in protection of epigenetic state. RNA spatially constrains CIZ1 assemblies via multivalent interactions at sub-nuclear sites. CIZ1 dimerizes to present dual extensions whose phosphorylation by AURKB dissolves RNA interaction in mitosis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/676856v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@107bec2org.highwire.dtl.DTLVardef@17cbb4aorg.highwire.dtl.DTLVardef@1ec0144org.highwire.dtl.DTLVardef@1474995_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Byrom, L., Turvey, G. L., Dowle, A. A., Thomas, M., Shiridkar, N., Green, B., Brown, M., Ball, C., Chapman, K. E., Guglielmi, E., Dickson, W., Noon, E., Sofi, S., Ainscough, J. F.-X., Antson, A. A., Coverley, D.. 2025-09-20. AURKB-driven dissolution of CIZ1-RNA assemblies from the inactive X chromosome in mitosis. https://doi.org/10.1101/2025.09.17.676856

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