Genome Wide Association Studies (GWAS) have identified single nucleotide polymorphisms within the IGF2 mRNA binding protein 2 (IGF2BP2/IMP2) gene that are associated with increased risk of Type 2 Diabetes (T2D). On a molecular level IMP2 is an mRNA binding protein that regulates translation through binding to untranslated regions (UTRs) of its target genes; however, the cellular function of IMP2 is unknown. Identifying IMP2 target genes and interrogating their functions may suggest the cellular function of IMP2. In pursuit of this goal a list of mRNAs bound by IMP2 was obtained using UV cross-linking followed by immunoprecipitation (CLIP). The list was then grouped into cellular processes using Gene Ontology (GO) term analysis. Among the top ranked GO processes were nitrogen metabolism, differentiation, cell death, proliferation, and lipid metabolism. Interestingly, the list of bound mRNAs contained four T2D associated genes including Lmna, Akt2, Bscl2, and Igf2bp2, itself. Though binding to putative target genes alone suggests regulation by IMP2, definitive regulation cannot be assumed. In order to validate regulation a priority set of 148 UTRs were PCR cloned into a luciferase reporter assay.
Future studies will use these UTRs in the luciferase reporter assay to determine whether and how (up or down) IMP2 regulates the identified target genes and to provide a more detailed description of the cellular utility of IMP2.
PROJECT: Identification and functional validation of IMP2 target genes