Association of AUUUA-binding protein with A+U-rich mRNA during nucleo-cytoplasmic transport

J Mol Biol. 1992 Aug 5;226(3):721-33. doi: 10.1016/0022-2836(92)90628-w.

Abstract

Resealed nuclear envelope (NE) vesicles from rat liver containing entrapped exogenous RNA were used to study the effect of adenosine+uridine binding factor (AUBF), present in cytosolic cell extracts, on ATP-dependent transport of A+U-rich RNA (AU+RNA) and A+U-free RNA (AU-RNA) across the NE. This factor specifically binds to A+U-rich sequences present in the 3' untranslated regions of lymphokine and cytokine mRNAs, containing overlapping AUUUA boxes (granulocyte-macrophage colony stimulating factor, interleukin-3). Addition of AUBF to the extravesicular compartment markedly increased the efflux of the in vitro transcribed, capped and polyadenylated AU+ RNAs. Export of entrapped AU- control RNA, such as beta-globin RNA, was not affected by AUBF, in contrast to chimeric AU+ beta-globin RNA containing the A+U-rich sequence of human interferon-alpha mRNA (6 reiterated AUUUA motifs). Competition experiments revealed that AUBF enhances the affinity of poly(A)-containing AU+ RNAs to the NE poly(A)-binding component (poly(A)-recognizing mRNA carrier p106), and thereby accelerates nuclear export of these RNAs. We could demonstrate that AUBF added to the extravesicular space forms stable complexes with polyadenylated AU+ RNA with relative molecular masses of about 45,000, 62,000 and 70,000 inside the vesicles or during ATP-dependent export. In addition we determined that AUBF may affect mRNA stability by protecting A+U-rich RNA against degradation by trans-acting, nuclear matrix-associated and A+U-specific endoribonuclease V.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine*
  • Animals
  • Base Sequence
  • Binding Sites
  • Carrier Proteins / metabolism
  • Cell Line
  • Cell Nucleus / metabolism*
  • Cytoplasm / metabolism
  • Endoribonucleases / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Interferon-alpha / genetics
  • Interleukin-3 / metabolism
  • Kinetics
  • Liver / metabolism*
  • Molecular Sequence Data
  • Nuclear Envelope / metabolism
  • Nuclear Matrix / metabolism
  • Plasmids
  • Polyribonucleotides / metabolism
  • Protein Binding
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins
  • Rats
  • Ribonucleoproteins / isolation & purification
  • Ribonucleoproteins / metabolism
  • Transcription, Genetic
  • Uridine*

Substances

  • Carrier Proteins
  • Interferon-alpha
  • Interleukin-3
  • Polyribonucleotides
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • adenosine-uridine binding factor
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Endoribonucleases
  • ribonuclease V
  • Adenosine
  • Uridine