Cell Division Requires RNA Eviction from Condensing Chromosomes

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2020 Oct 14

PMID 33053167

Citations 17

Authors

Judith A Sharp

Carlos Perea-Resa

Wei Wang

Michael D Blower

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

An atlas of RNA-dependent proteins in cell division reveals the riboregulation of mitotic protein-protein interactions.

Rajagopal V, Seiler J, Nasa I, Cantarella S, Theiss J, Herget F Nat Commun. 2025; 16(1):2325.

PMID: 40057470 PMC: 11890761. DOI: 10.1038/s41467-025-57671-3.

An atlas of RNA-dependent proteins in cell division reveals the riboregulation of mitotic protein-protein interactions.

Rajagopal V, Seiler J, Nasa I, Cantarella S, Theiss J, Herget F bioRxiv. 2024; .

PMID: 39386702 PMC: 11463612. DOI: 10.1101/2024.09.25.614981.

Role of the SAF-A SAP domain in X inactivation, transcription, splicing, and cell proliferation.

Sharp J, Sparago E, Thomas R, Alimenti K, Wang W, Blower M bioRxiv. 2024; .

PMID: 39314300 PMC: 11419091. DOI: 10.1101/2024.09.09.612041.

Spatial omics advances for in situ RNA biology.

Ren J, Luo S, Shi H, Wang X Mol Cell. 2024; 84(19):3737-3757.

PMID: 39270643 PMC: 11455602. DOI: 10.1016/j.molcel.2024.08.002.

Deciphering the phospho-signature induced by hepatitis B virus in primary human hepatocytes.

Pastor F, Charles E, Belmudes L, Chabrolles H, Cescato M, Rivoire M Front Microbiol. 2024; 15:1415449.

PMID: 38841065 PMC: 11150682. DOI: 10.3389/fmicb.2024.1415449.

References

Petrov D, Margreitter C, Grandits M, Oostenbrink C, Zagrovic B . A systematic framework for molecular dynamics simulations of protein post-translational modifications. PLoS Comput Biol. 2013; 9(7):e1003154. PMC: 3715417. DOI: 10.1371/journal.pcbi.1003154. View

Hengeveld R, Hertz N, Vromans M, Zhang C, Burlingame A, Shokat K . Development of a chemical genetic approach for human aurora B kinase identifies novel substrates of the chromosomal passenger complex. Mol Cell Proteomics. 2012; 11(5):47-59. PMC: 3418839. DOI: 10.1074/mcp.M111.013912. View

Boke E, Ruer M, Wuhr M, Coughlin M, Lemaitre R, Gygi S . Amyloid-like Self-Assembly of a Cellular Compartment. Cell. 2016; 166(3):637-650. PMC: 5082712. DOI: 10.1016/j.cell.2016.06.051. View

Ohta S, Bukowski-Wills J, Sanchez-Pulido L, de Lima Alves F, Wood L, Chen Z . The protein composition of mitotic chromosomes determined using multiclassifier combinatorial proteomics. Cell. 2010; 142(5):810-21. PMC: 2982257. DOI: 10.1016/j.cell.2010.07.047. View

Wang K, Chang H . Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011; 43(6):904-14. PMC: 3199020. DOI: 10.1016/j.molcel.2011.08.018. View

Shin J, Kim T, Kim H, Kim H, Suh M, Lee S . Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells. Elife. 2016; 5:e10877. PMC: 4798952. DOI: 10.7554/eLife.10877. View

Putkey F, Cramer T, Morphew M, Silk A, Johnson R, McIntosh J . Unstable kinetochore-microtubule capture and chromosomal instability following deletion of CENP-E. Dev Cell. 2002; 3(3):351-65. DOI: 10.1016/s1534-5807(02)00255-1. View

Jao C, Salic A . Exploring RNA transcription and turnover in vivo by using click chemistry. Proc Natl Acad Sci U S A. 2008; 105(41):15779-84. PMC: 2572917. DOI: 10.1073/pnas.0808480105. View

Dreyfuss G, Choi Y, Adam S . Characterization of heterogeneous nuclear RNA-protein complexes in vivo with monoclonal antibodies. Mol Cell Biol. 1984; 4(6):1104-14. PMC: 368879. DOI: 10.1128/mcb.4.6.1104-1114.1984. View

10.

Huelga S, Vu A, Arnold J, Liang T, Liu P, Yan B . Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins. Cell Rep. 2012; 1(2):167-78. PMC: 3345519. DOI: 10.1016/j.celrep.2012.02.001. View

11.

Komarov P, Komarova E, Kondratov R, Coon J, Chernov M, Gudkov A . A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science. 1999; 285(5434):1733-7. DOI: 10.1126/science.285.5434.1733. View

12.

Stumpff J, Wagenbach M, Franck A, Asbury C, Wordeman L . Kif18A and chromokinesins confine centromere movements via microtubule growth suppression and spatial control of kinetochore tension. Dev Cell. 2012; 22(5):1017-29. PMC: 3356572. DOI: 10.1016/j.devcel.2012.02.013. View

13.

Hasegawa Y, Brockdorff N, Kawano S, Tsutui K, Tsutui K, Nakagawa S . The matrix protein hnRNP U is required for chromosomal localization of Xist RNA. Dev Cell. 2010; 19(3):469-76. DOI: 10.1016/j.devcel.2010.08.006. View

14.

Clemson C, McNeil J, Willard H, Lawrence J . XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J Cell Biol. 1996; 132(3):259-75. PMC: 2120729. DOI: 10.1083/jcb.132.3.259. View

15.

Rao S, Huang S, St Hilaire B, Engreitz J, Perez E, Kieffer-Kwon K . Cohesin Loss Eliminates All Loop Domains. Cell. 2017; 171(2):305-320.e24. PMC: 5846482. DOI: 10.1016/j.cell.2017.09.026. View

16.

Levesque A, Compton D . The chromokinesin Kid is necessary for chromosome arm orientation and oscillation, but not congression, on mitotic spindles. J Cell Biol. 2001; 154(6):1135-46. PMC: 2150818. DOI: 10.1083/jcb.200106093. View

17.

Kettenbach A, Schweppe D, Faherty B, Pechenick D, Pletnev A, Gerber S . Quantitative phosphoproteomics identifies substrates and functional modules of Aurora and Polo-like kinase activities in mitotic cells. Sci Signal. 2011; 4(179):rs5. PMC: 3808085. DOI: 10.1126/scisignal.2001497. View

18.

Gibcus J, Samejima K, Goloborodko A, Samejima I, Naumova N, Nuebler J . A pathway for mitotic chromosome formation. Science. 2018; 359(6376). PMC: 5924687. DOI: 10.1126/science.aao6135. View

19.

Olsen J, Vermeulen M, Santamaria A, Kumar C, Miller M, Jensen L . Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010; 3(104):ra3. DOI: 10.1126/scisignal.2000475. View

20.

Okubo S, Hara F, Tsuchida Y, Shimotakahara S, Suzuki S, Hatanaka H . NMR structure of the N-terminal domain of SUMO ligase PIAS1 and its interaction with tumor suppressor p53 and A/T-rich DNA oligomers. J Biol Chem. 2004; 279(30):31455-61. DOI: 10.1074/jbc.M403561200. View