Characterization of the RNA recognition mode of hnRNP G extends its role in SMN2 splicing regulation

Nucleic Acids Res. 2014 Jun;42(10):6659-72. doi: 10.1093/nar/gku244. Epub 2014 Apr 1.


Regulation of SMN2 exon 7 splicing is crucial for the production of active SMN protein and the survival of Spinal Muscular Atrophy (SMA) patients. One of the most efficient activators of exon 7 inclusion is hnRNP G, which is recruited to the exon by Tra2-β1. We report that in addition to the C-terminal region of hnRNP G, the RNA Recognition Motif (RRM) and the middle part of the protein containing the Arg-Gly-Gly (RGG) box are important for this function. To better understand the mode of action of hnRNP G in this context we determined the structure of its RRM bound to an SMN2 derived RNA. The RRM interacts with a 5'-AAN-3' motif and specifically recognizes the two consecutive adenines. By testing the effect of mutations in hnRNP G RRM and in its putative binding sites on the splicing of SMN2 exon 7, we show that it specifically binds to exon 7. This interaction is required for hnRNP G splicing activity and we propose its recruitment to a polyA tract located upstream of the Tra2-β1 binding site. Finally, our data suggest that hnRNP G plays a major role in the recruitment of the Tra2-β1/hnRNP G/SRSF9 trimeric complex to SMN2 exon 7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / chemistry
  • Amino Acid Motifs
  • Binding Sites
  • Exons
  • HEK293 Cells
  • Heterogeneous-Nuclear Ribonucleoproteins / chemistry*
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism*
  • Humans
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA / chemistry*
  • RNA / metabolism*
  • RNA Splicing*
  • RNA-Binding Proteins / metabolism
  • Survival of Motor Neuron 2 Protein / genetics*
  • Survival of Motor Neuron 2 Protein / metabolism


  • Heterogeneous-Nuclear Ribonucleoproteins
  • RBMX protein, human
  • RNA-Binding Proteins
  • Survival of Motor Neuron 2 Protein
  • RNA
  • Adenine

Associated data

  • PDB/2MB0