Dual localization of the RNA binding protein CUGBP-1 to stress granule and perinucleolar compartment

Exp Cell Res. 2008 Feb 1;314(3):543-53. doi: 10.1016/j.yexcr.2007.10.024. Epub 2007 Nov 12.

Abstract

The mRNA-binding protein CUGBP-1 is a multi-faceted factor, involved in a wide range of biological processes including splicing, translation initiation and mRNA degradation. Here we show that CUGBP-1 is a novel constituent of stress granule (SG), the translational silencing machinery assembled in response to environmental stress. CUGBP-1 was rapidly routed to SGs upon exposure to a variety of environmental stress, and actively shuttles between the nucleus and SGs. The linker domain located between the second and third RNA recognition motifs (RRMs) was found to be essential for the recruitment of CUGBP-1 to SGs. Importantly, we discovered that the linker domain is also required to direct CUGBP-1 to another subcellular structure, perinucleolar compartment (PNC). These results demonstrate the dynamic behavior of CUGBP-1 during stress response and that the linker region, in concert with RRMs, plays a significant role in defining its subcellular localization and dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Amino Acid Motifs / genetics
  • CELF1 Protein
  • Cell Compartmentation / genetics*
  • Cell Nucleolus / genetics
  • Cell Nucleolus / metabolism*
  • Cell Nucleolus / ultrastructure
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Cytoplasmic Granules / genetics
  • Cytoplasmic Granules / metabolism*
  • Cytoplasmic Granules / ultrastructure
  • HeLa Cells
  • Humans
  • Poly(A)-Binding Proteins / genetics
  • Poly(A)-Binding Proteins / metabolism
  • Protein Structure, Tertiary / genetics
  • Protein Transport / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Stress, Physiological / genetics
  • Stress, Physiological / metabolism*
  • Stress, Physiological / physiopathology
  • T-Cell Intracellular Antigen-1

Substances

  • CELF1 Protein
  • CELF1 protein, human
  • Poly(A)-Binding Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • T-Cell Intracellular Antigen-1
  • TIA1 protein, human