Arginine methylation of ubiquitin-associated protein 2-like is required for the accurate distribution of chromosomes

FASEB J. 2016 Jan;30(1):312-23. doi: 10.1096/fj.14-268987. Epub 2015 Sep 17.

Abstract

Proper bioriented attachment of microtubules and kinetochores is essential for the precise distribution of duplicated chromosomes to each daughter cell. An aberrant kinetochore-microtubule attachment results in chromosome instability, which leads to cellular transformation or apoptosis. In this article, we show that ubiquitin-associated protein 2-like (UBAP2L) is necessary for correct kinetochore-microtubule attachment. Depletion of UBAP2L inhibited chromosome alignment in metaphase and delayed progression to anaphase by activating spindle assembly checkpoint signaling. In addition, UBAP2L knockdown increased side-on attachment of kinetochores along the microtubules and suppressed stable kinetochore fiber formation. A proteomics analysis identified protein arginine methyltransferase (PRMT)1 as a direct interaction partner of UBAP2L. UBAP2L has an arginine- and glycine-rich motif called the RGG/RG or GAR motif in the N terminus. Biochemical analysis confirmed that arginine residues in the RGG/RG motif of UBAP2L were directly methylated by PRMT1. Finally, we demonstrated that the RGG/RG motif of UBAP2L is essential for the proper alignment of chromosomes in metaphase for the accurate distribution of chromosomes. Our results show a possible role for arginine methylation in UBAP2L for the progression of mitosis.

Keywords: PRMT1; UBAP2L; kinetochore; mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Arginine / metabolism
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • Methylation
  • Microtubules / metabolism
  • Protein Binding
  • Protein Processing, Post-Translational*
  • Protein Structure, Tertiary
  • Protein-Arginine N-Methyltransferases / chemistry
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism

Substances

  • Carrier Proteins
  • Repressor Proteins
  • Ubap2L protein, human
  • Arginine
  • PRMT1 protein, human
  • Protein-Arginine N-Methyltransferases