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UBL5 is essential for pre-mRNA splicing and sister chromatid cohesion in human cells

Y. Oka, H. Varmark, K. Vitting-Seerup, P. Beli, J. Waage, A. Hakobyan, M. Mistrik, C. Choudhary, M. Rohde, S. Bekker-Jensen, N. Mailand,

. 2014 ; 15 (9) : 956-64.

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc15023171

UBL5 is an atypical ubiquitin-like protein, whose function in metazoans remains largely unexplored. We show that UBL5 is required for sister chromatid cohesion maintenance in human cells. UBL5 primarily associates with spliceosomal proteins, and UBL5 depletion decreases pre-mRNA splicing efficiency, leading to globally enhanced intron retention. Defective sister chromatid cohesion is a general consequence of dysfunctional pre-mRNA splicing, resulting from the selective downregulation of the cohesion protection factor Sororin. As the UBL5 yeast orthologue, Hub1, also promotes spliceosome functions, our results show that UBL5 plays an evolutionary conserved role in pre-mRNA splicing, the integrity of which is essential for the fidelity of chromosome segregation.

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$a Varmark, Hanne $u Ubiquitin Signaling Group, Department of Disease Biology, The Novo Nordisk Foundation Center for Protein Research University of Copenhagen, Copenhagen, Denmark.
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$a Vitting-Seerup, Kristoffer $u Bioinformatics Centre, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
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$a Beli, Petra $u Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark Institute of Molecular Biology (IMB), Mainz, Germany.
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$a Waage, Johannes $u Bioinformatics Centre, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
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$a Hakobyan, Anna $u Department of Cell Death and Metabolism, Danish Cancer Society Research Center, Copenhagen, Denmark.
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$a Mistrik, Martin $u Institute of Molecular and Translational Medicine, Palacky University, Olomouc, Czech Republic.
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$a Choudhary, Chunaram $u Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
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$a Rohde, Mikkel $u Department of Cell Death and Metabolism, Danish Cancer Society Research Center, Copenhagen, Denmark.
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$a Bekker-Jensen, Simon $u Ubiquitin Signaling Group, Department of Disease Biology, The Novo Nordisk Foundation Center for Protein Research University of Copenhagen, Copenhagen, Denmark.
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