Structural basis for the dual RNA-recognition modes of human Tra2-β RRM

Nucleic Acids Res. 2011 Mar;39(4):1538-53. doi: 10.1093/nar/gkq854. Epub 2010 Oct 5.


Human Transformer2-β (hTra2-β) is an important member of the serine/arginine-rich protein family, and contains one RNA recognition motif (RRM). It controls the alternative splicing of several pre-mRNAs, including those of the calcitonin/calcitonin gene-related peptide (CGRP), the survival motor neuron 1 (SMN1) protein and the tau protein. Accordingly, the RRM of hTra2-β specifically binds to two types of RNA sequences [the CAA and (GAA)(2) sequences]. We determined the solution structure of the hTra2-β RRM (spanning residues Asn110-Thr201), which not only has a canonical RRM fold, but also an unusual alignment of the aromatic amino acids on the β-sheet surface. We then solved the complex structure of the hTra2-β RRM with the (GAA)(2) sequence, and found that the AGAA tetra-nucleotide was specifically recognized through hydrogen-bond formation with several amino acids on the N- and C-terminal extensions, as well as stacking interactions mediated by the unusually aligned aromatic rings on the β-sheet surface. Further NMR experiments revealed that the hTra2-β RRM recognizes the CAA sequence when it is integrated in the stem-loop structure. This study indicates that the hTra2-β RRM recognizes two types of RNA sequences in different RNA binding modes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Base Sequence
  • Guanine / chemistry
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry*
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • RNA / chemistry*
  • RNA-Binding Proteins / chemistry*
  • Serine-Arginine Splicing Factors


  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • TRA2B protein, human
  • Serine-Arginine Splicing Factors
  • Guanine
  • RNA

Associated data

  • PDB/2RRA
  • PDB/2RRB