Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU

Mol Cell. 2004 Jan 16;13(1):101-11. doi: 10.1016/s1097-2765(03)00481-7.

Abstract

The AU-rich element (ARE) in the 3' untranslated region of unstable mRNAs mediate their rapid degradation. ARE binding proteins (AUBPs) have been described that either stabilize or otherwise degrade ARE-mRNAs by recruiting the exosome, a complex of 3'-to-5' exoribonucleases. We have identified RHAU, a putative DExH RNA helicase that was isolated in association with the ARE of urokinase plasminogen activator mRNA (ARE(uPA)). RHAU physically interacts with the deadenylase PARN and the human exosome and enhances the deadenylation and decay of ARE(uPA)-mRNAs. An alternatively spliced isoform of RHAU that localized to the cytoplasm had a more pronounced effect on ARE(uPA)-mRNA destabilization than full-length RHAU. Furthermore, the ATPase activity of RHAU is essential for its mRNA-destabilizing function. ARE(uPA)-mRNA recognition by RHAU may be mediated through its RNA-dependent interaction with the AUBPs HuR and NFAR1. A model is presented to describe the action of RHAU in ARE(uPA)-directed mRNA turnover.

MeSH terms

  • 3' Untranslated Regions
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Alternative Splicing
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Antigens, Surface*
  • Conserved Sequence
  • Cytoplasm / metabolism
  • Down-Regulation
  • ELAV Proteins
  • ELAV-Like Protein 1
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism*
  • Glutathione Transferase / metabolism
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Nuclear Factor 90 Proteins
  • Phosphoproteins*
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • RNA Helicases / chemistry*
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • RNA Stability
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Urokinase-Type Plasminogen Activator / metabolism

Substances

  • 3' Untranslated Regions
  • Antigens, Surface
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • ILF3 protein, human
  • Nuclear Factor 90 Proteins
  • Phosphoproteins
  • Protein Isoforms
  • RNA, Messenger
  • RNA-Binding Proteins
  • Recombinant Proteins
  • Adenosine Triphosphate
  • Glutathione Transferase
  • Exoribonucleases
  • Urokinase-Type Plasminogen Activator
  • Adenosine Triphosphatases
  • RNA Helicases

Associated data

  • GENBANK/AJ577133
  • GENBANK/AJ577134