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

Yasuyoshi Oka, Hanne Varmark, Kristoffer Vitting-Seerup, Petra Beli, Johannes Eichler Waage, Anna Hakobyan, Martin Mistrik, Chuna Ram Choudhary, Mikkel Rohde, Simon Bekker-Jensen, Niels Mailand

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalE M B O Reports
Volume15
Issue number9
Pages (from-to)956-964
Number of pages9
ISSN1469-221X
DOIs
Publication statusPublished - Sept 2014

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