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

EMBO Rep. 2014 Sep;15(9):956-64. doi: 10.15252/embr.201438679. Epub 2014 Aug 4.


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.

Keywords: UBL5; pre‐mRNA splicing; sister chromatid cohesion; sororin; ubiquitin‐like protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Cell Cycle Proteins / genetics*
  • Chromatids / genetics
  • Chromosome Segregation / genetics
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Ligases / genetics
  • Mitosis / genetics
  • RNA Precursors / genetics*
  • RNA Splicing / genetics*
  • Saccharomyces cerevisiae Proteins / genetics
  • Spliceosomes / genetics
  • Ubiquitins / genetics*
  • Ubiquitins / metabolism


  • Adaptor Proteins, Signal Transducing
  • CDCA5 protein, human
  • Cell Cycle Proteins
  • Eye Proteins
  • RNA Precursors
  • Saccharomyces cerevisiae Proteins
  • UBL5 protein, human
  • Ubiquitins
  • Ligases
  • HUB1 protein, S cerevisiae