Cell Reports: IGF2BP3 modulates the interaction of invasion-associated transcripts with RISC
Hanane Ennajdaoui, Jonathan M Howard, Timothy Sterne-Weiler, Fereshteh Jahanbani, Doyle J Coyne, Philip J Uren, Marija Dargyte, Sol Katzman, Jolene M Draper, Andrew Wallace, Oscar Cazarez, Suzanne C Burns, Mei Qiao, Lindsay Hinck, Andrew D Smith, Masoud M Toloue, Benjamin J Blencowe, Luiz OF Penalva, Jeremy R Sanford
Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy, but its role(s) in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation, and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual nucleotide resolution crosslinking immunoprecipitation (iCLIP) revealed a significant overlap of IGF2BP3 and microRNA (miRNA) binding sites. IGF2BP3 promotes the association of the RNA-induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating …
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