hnRNP A1 Selectively Interacts Through Its Gly-rich Domain With Different RNA-binding Proteins

J Mol Biol. 1996 Jun 14;259(3):337-48. doi: 10.1006/jmbi.1996.0324.

Abstract

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are abundant nuclear polypeptides, most likely involved in different steps of pre-mRNA processing. Protein A1 (34 kDa), a prominent member of the hnRNP family, seems to act by modulating the RNA secondary structure and by antagonizing some splicing factors (SR proteins) in splice-site selection and exon skipping/inclusion. A role of A1 in the nucleo-cytoplasmic transport of RNA has also been proposed. These activities might depend not only on the RNA-binding properties of the protein but also on specific protein-protein interactions. Here we report that A1 can indeed selectively interact, in vitro, both with itself and with other hnRNP basic "core" proteins. Such selective binding is mediated exclusively by the Gly-rich C-terminal domain, where a novel protein-binding motif constituted by hydrophobic repeats can be envisaged. The same domain is necessary and sufficient to promote specific interaction in vivo, as assayed by the yeast two-hybrid assay. Moreover, an in vitro interaction with some SR proteins was also observed. These observations suggest that diverse and specific protein-protein interactions might contribute to the different functions of the hnRNP A1 protein in mRNA maturation.

MeSH terms

  • Amino Acid Sequence
  • Arginine / metabolism
  • Base Sequence
  • Binding Sites
  • Glycine / chemistry
  • Glycine / metabolism
  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B*
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acids / chemistry
  • Nucleic Acids / metabolism
  • Phenols / chemistry
  • Protein Conformation
  • RNA Splicing
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Ribonucleoproteins / chemistry
  • Ribonucleoproteins / metabolism*
  • Serine / metabolism
  • Structure-Activity Relationship
  • Substrate Specificity
  • Yeasts / metabolism

Substances

  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Nucleic Acids
  • Phenols
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Ribonucleoproteins
  • Serine
  • Arginine
  • Glycine