P21 Functions to Prevent Radiation-induced Myocardial Injury in Mice

Abstract

Materials/Methods: We determined the minimal nucleotide recognition element (RE) of the prototypical IMP protein, IMP1, using gel mobility shift assays, in-vitro selection, and NMR spectroscopy. We identified conserved transcripts containing the IMP1 RE by Sequel query of the UCSC 3 UTR database (hg19/mm8); we further performed immunoprecipitation and qRT-PCR detection of IMP1 associated mRNAs from mouse embryonic cells. Ingenuity pathway analysis v9.0 was used to explore functional relationships between proteins encoded by the mRNA ligands of IMP1; P values are based on a right-tailed Fisher’s exact test. Results: The third and fourth hnRNP K homology domains of IMP1 specifically recognize a bipartite RE: a 5 element, CGGAC, followed by a variable 3 element, C/A-CA-C/U. The IMP1 consensus REs are evolutionarily conserved in the 3 UTRs of 114 transcripts. Approximately 70% of these transcripts (17 of 25 tested) are enriched over fourfold in IMP1 immunoprecipitates. Gene ontology analysis of predicted IMP1 ligands reveals enrichment of gene-networks controlling cell survival (n Z 33, p < 0.0001) and differentiation (n Z 28, p < 0.005). Aberrant transcription of IMP1 RNA ligands (n Z 13) has been demonstrated in neoplastic conditions including ovarian cancer, papillary thyroid carcinoma, NSCLC, DLBCL, and melanoma (p < 0.0050.01, Table).