Mammalian pre-mRNA 3' end processing factor CF I m 68 functions in mRNA export

Mol Biol Cell. 2009 Dec;20(24):5211-23. doi: 10.1091/mbc.e09-05-0389.

Abstract

Export of mRNA from the nucleus is linked to proper processing and packaging into ribonucleoprotein complexes. Although several observations indicate a coupling between mRNA 3' end formation and export, it is not known how these two processes are mechanistically connected. Here, we show that a subunit of the mammalian pre-mRNA 3' end processing complex, CF I(m)68, stimulates mRNA export. CF I(m)68 shuttles between the nucleus and the cytoplasm in a transcription-dependent manner and interacts with the mRNA export receptor NXF1/TAP. Consistent with the idea that CF I(m)68 may act as a novel adaptor for NXF1/TAP, we show that CF I(m)68 promotes the export of a reporter mRNA as well as of endogenous mRNAs, whereas silencing by RNAi results in the accumulation of mRNAs in the nucleus. Moreover, CF I(m)68 associates with 80S ribosomes but not polysomes, suggesting that it is part of the mRNP that is remodeled in the cytoplasm during the initial stages of translation. These results reveal a novel function for the pre-mRNA 3' end processing factor CF I(m)68 in mRNA export.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Nucleus / metabolism
  • Centrifugation, Density Gradient
  • HeLa Cells
  • Humans
  • Karyopherins / metabolism
  • Mice
  • Models, Biological
  • NIH 3T3 Cells
  • Nucleocytoplasmic Transport Proteins / metabolism
  • Protein Binding
  • Protein Subunits / metabolism
  • RNA 3' End Processing*
  • RNA Precursors / metabolism*
  • RNA Transport*
  • RNA-Binding Proteins / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Ribonucleoproteins / metabolism
  • Ribosomes / metabolism
  • Transcription, Genetic
  • mRNA Cleavage and Polyadenylation Factors / metabolism*

Substances

  • Karyopherins
  • NXF1 protein, human
  • Nucleocytoplasmic Transport Proteins
  • Protein Subunits
  • RNA Precursors
  • RNA-Binding Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Ribonucleoproteins
  • cleavage factor Im, human
  • exportin 1 protein
  • mRNA Cleavage and Polyadenylation Factors
  • messenger ribonucleoprotein