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PreprintCited by 2Genomics and Chromatin DynamicsGenetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesNuclear Structure and Function

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

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Byrom, Lewis, Turvey, Gabrielle L., Dowle, Adam A., Thomas, Megan, Shirodkar, Navin, Green, Ben J., Brown, Maxwell, Ball, Charlotte, Chapman, Kate E., Guglielmi, Elena, Dickson, William, Noon, Emma, Sofi, Sajad, Ainscough, Justin F-X., Antson, Alfred A., Coverley, Dawn·2025·Nucleic Acids Research
DOI 10.1101/2025.09.17.676856PMC PMC12862363

Preprint — published as 10.1093/nar/gkag018 · Paper page

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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. Bullets: The 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:

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Metadata

Authors
Byrom, L., Turvey, G. L., Dowle, A. A., Thomas, M., Shirodkar, N., Green, B. J., Brown, M., Ball, C., Chapman, K. E., Guglielmi, E., Dickson, W., Noon, E., Sofi, S., Ainscough, J. F.-X., Antson, A. A., & Coverley, D.
Affiliations
University of York (GB)
Corresponding author
  • Byrom, Lewis
  • Coverley, Dawn
ORCID
Venue
Nucleic Acids Research
Publisher
openRxiv
Published
2025-09-20
Volume
54
Issue
3
ISSN
0305-1048 (ISSN-L)
DOI
10.1101/2025.09.17.676856
PMC
PMC12862363
OpenAlex
W7127184437
Cited by
2
References
1
Citations by year
2026: 2
FWCI
4.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
Funders
  • Wellcome Trust (224665)
  • Leverhulme Trust
  • Medical Research Council (MR/V029088/1, MR/V029088)
  • Engineering and Physical Sciences Research Council (EP/M028127/1, EP/K039660/1)
  • Biotechnology and Biological Sciences Research Council (EP/M028127/1, EP/K039660/1, BB/T007222/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
CIZ1, Aurora B kinase, inactive X chromosome, mitosis, prometaphase, RNA-protein interactions, chromatin, nuclear matrix, epigenetic stability, protein phosphorylation, phosphomimetic mutations
MeSH terms
Animals, Chromatin, Humans, Mitosis, Nuclear Proteins, X Chromosome, RNA-Binding Proteins, Nuclear Matrix-Associated Proteins, X Chromosome Inactivation, Mice, RNA, Long Noncoding, Aurora Kinase B

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