Two isoforms of the mRNA binding protein IGF2BP2 are generated by alternative translational initiation

PLoS One. 2012;7(3):e33140. doi: 10.1371/journal.pone.0033140. Epub 2012 Mar 12.


IGF2BP2 is a member of a family of mRNA binding proteins that, collectively, have been shown to bind to several different mRNAs in mammalian cells, including one of the mRNAs encoding insulin-like growth factor-2. Polymorphisms in the Igf2bp2 gene are associated with risk of developing type 2 diabetes, but detailed functional characterisation of IGF2BP2 protein is lacking. By immunoblotting with C-terminally reactive antibodies we identified a novel IGF2BP2 isoform with a molecular weight of 58 kDa in both human and rodents, that is expressed at somewhat lower levels than the full-length 65 kDa protein. We demonstrated by mutagenesis that this isoform is generated by alternative translation initiation at the internal Met69. It lacks a conserved N-terminal RNA Recognition Motif (RRM) and would be predicted to differ functionally from the canonical full length isoform. We further investigated IGF2BP2 mRNA transcripts by amplification of cDNA using 5'-RACE. We identified multiple transcription start sites of the human, mouse and rat Igf2bp2 genes in a highly conserved region only 50-90 nts upstream of the major translation start site, ruling out the existence of N-terminally extended isoforms. We conclude that structural heterogeneity of IGF2BP2 protein should be taken into account when considering cellular function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • DNA, Complementary / genetics
  • Humans
  • Mice
  • Molecular Sequence Data
  • Mutagenesis
  • Peptide Chain Initiation, Translational / genetics
  • Peptide Chain Initiation, Translational / physiology*
  • Protein Isoforms / genetics*
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Rats
  • Sequence Analysis, DNA
  • Species Specificity
  • Transcription Initiation Site


  • DNA, Complementary
  • IGF2BP2 protein, human
  • IGF2BP2 protein, mouse
  • Protein Isoforms
  • RNA-Binding Proteins