Overexpression of MLN51 triggers P-body disassembly and formation of a new type of RNA granules

J Cell Sci. 2014 Nov 1;127(Pt 21):4692-701. doi: 10.1242/jcs.154500. Epub 2014 Sep 9.

Abstract

Metastatic lymph node 51 (MLN51, also known as CASC3) is a core component of the exon junction complex (EJC), which is loaded onto spliced mRNAs and plays an essential role in determining their fate. Unlike the three other EJC core components [eIF4AIII, Magoh and Y14 (also known as RBM8A)], MLN51 is mainly located in the cytoplasm, where it plays a key role in the assembly of stress granules. In this study, we further investigated the cytoplasmic role of MLN51. We show that MLN51 is a new component of processing bodies (P-bodies). When overexpressed, MLN51 localizes in novel small cytoplasmic foci. These contain RNA, show directed movements and are distinct from stress granules and P-bodies. The appearance of these foci correlates with the process of P-body disassembly. A similar reduction in P-body count is also observed in human HER2-positive (HER2(+)) breast cancer cells overexpressing MLN51. This suggests that P-body disassembly and subsequent mRNA deregulation might correlate with cancer progression.

Keywords: Breast cancer; MLN51; P-bodies; Stress granules; mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cytoplasm / metabolism
  • Cytoplasmic Granules / genetics
  • Cytoplasmic Granules / metabolism*
  • Eukaryotic Initiation Factor-4A / genetics
  • Eukaryotic Initiation Factor-4A / metabolism
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism

Substances

  • CASC3 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • RBM8A protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Eukaryotic Initiation Factor-4A