CDK13, a Kinase Involved in Pre-mRNA Splicing, Is a Component of the Perinucleolar Compartment

PLoS One. 2016 Feb 17;11(2):e0149184. doi: 10.1371/journal.pone.0149184. eCollection 2016.

Abstract

The perinucleolar compartment (PNC) is a subnuclear stucture forming predominantly in cancer cells; its prevalence positively correlates with metastatic capacity. Although several RNA-binding proteins have been characterized in PNC, the molecular function of this compartment remains unclear. Here we demonstrate that the cyclin-dependent kinase 13 (CDK13) is a newly identified constituent of PNC. CDK13 is a kinase involved in the regulation of gene expression and whose overexpression was found to alter pre-mRNA processing. In this study we show that CDK13 is enriched in PNC and co-localizes all along the cell cycle with the PNC component PTB. In contrast, neither the cyclins K and L, known to associate with CDK13, nor the potential kinase substrates accumulate in PNC. We further show that CDK13 overexpression increases PNC prevalence suggesting that CDK13 may be determinant for PNC formation. This result linked to the finding that CDK13 gene is amplified in different types of cancer indicate that this kinase can contribute to cancer development in human.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CDC2 Protein Kinase / chemistry
  • CDC2 Protein Kinase / metabolism*
  • Cell Compartmentation*
  • Cell Line, Tumor
  • Cell Nucleolus / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cyclins / metabolism
  • Humans
  • Mitosis
  • Nucleolin
  • Phosphoproteins / metabolism
  • Protein Structure, Tertiary
  • RNA Precursors / genetics*
  • RNA Precursors / metabolism
  • RNA Splicing / genetics*
  • RNA-Binding Proteins / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • Cyclins
  • Phosphoproteins
  • RNA Precursors
  • RNA-Binding Proteins
  • fibrillarin
  • CDC2 Protein Kinase
  • CDK13 protein, human

Grants and funding

This work was funded by grants from Cancer Research foundations, “Association pour la Recherche sur le Cancer” (ARC 5290), and “Ligue contre le cancer” Languedoc-Roussillon (LR). Y. Even received short-term fellowships from the “Fondation pour la Recherche Médicale”, “Ligue contre le cancer” LR and Soroptimist. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.