A molecular link between SR protein dephosphorylation and mRNA export

Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9666-70. doi: 10.1073/pnas.0403533101. Epub 2004 Jun 21.

Abstract

In metazoans, multiple RNA-binding proteins, including the shuttling serine/arginine-rich (SR)-splicing factors, function as adapters for mRNA nuclear export by interacting with the export receptor TAP/nuclear export factor 1 (NXF1). Yet, it is unclear how interactions between adapters and TAP are regulated. Here, we demonstrate that the SR proteins 9G8 and ASF/SF2 exhibit higher affinity for TAP/NXF1 when hypophosphorylated. 9G8 is recruited to the pre-mRNA in a hyperphosphorylated form but becomes hypophosphorylated during splicing both in vivo and in vitro. TAP preferentially binds spliced mRNA-protein complexes compared with pre-mRNA-protein complexes. Thus, the phosphorylation state of the SR protein adapters may underlie the selectivity of TAP-mediated export of spliced mRNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Catalysis
  • HeLa Cells
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nucleocytoplasmic Transport Proteins / genetics
  • Nucleocytoplasmic Transport Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • RNA Splicing*
  • RNA Transport*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism
  • Serine-Arginine Splicing Factors
  • Substrate Specificity

Substances

  • NXF1 protein, human
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • messenger ribonucleoprotein
  • Serine-Arginine Splicing Factors