IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC | Zendy

Hanane Ennajdaoui | Zendy; Jonathan M. Howard | Zendy; Timothy Sterne-Weiler | Zendy; Fereshteh Jahanbani | Zendy; Doyle Coyne | Zendy; Philip J. Uren | Zendy; Marija Dargyte | Zendy; Sol Katzman | Zendy; Jolene M. Draper | Zendy; Andrew Wallace | Zendy; Oscar Cazarez | Zendy; Suzanne Burns | Zendy; Mei Qiao | Zendy; Lindsay Hinck | Zendy; Andrew D. Smith | Zendy; Masoud Toloue | Zendy; Benjamin J. Blencowe | Zendy; Luiz O. F. Penalva | Zendy; Jeremy R. Sanford | Zendy

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IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC

Author(s) -

Hanane Ennajdaoui,

Jonathan M. Howard,

Timothy Sterne-Weiler,

Fereshteh Jahanbani,

Doyle Coyne,

Philip J. Uren,

Marija Dargyte,

Sol Katzman,

Jolene M. Draper,

Andrew Wallace,

Oscar Cazarez,

Suzanne Burns,

Mei Qiao,

Lindsay Hinck,

Andrew D. Smith,

Masoud Toloue,

Benjamin J. Blencowe,

Luiz O. F. Penalva,

Jeremy R. Sanford

Publication year - 2016

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.04.083

Subject(s) - gene knockdown , gene silencing , microrna , rna binding protein , cancer research , rna , messenger rna , biology , gene , genetics

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 significant overlap of IGF2BP3 and microRNA (miRNA) binding sites. IGF2BP3 promotes association of the RNA-induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions.

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