Cell Reports
(May 2016)
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 O.F. Penalva,
Jeremy R. Sanford
Affiliations
Hanane Ennajdaoui
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA
Jonathan M. Howard
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA
Timothy Sterne-Weiler
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA
Fereshteh Jahanbani
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA
Doyle J. Coyne
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA
Philip J. Uren
Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
Marija Dargyte
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA
Sol Katzman
Center for Biomolecular Science and Engineering, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA
Jolene M. Draper
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA
Andrew Wallace
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA
Oscar Cazarez
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA
Suzanne C. Burns
Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Mei Qiao
Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Lindsay Hinck
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA
Andrew D. Smith
Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
Masoud M. Toloue
Bioo Scientific Corporation, 7500 Burleston Road, Austin, TX 78744, USA
Benjamin J. Blencowe
The Donnelly Centre, University of Toronto, Toronto, ON M5S 1A1, Canada
Luiz O.F. Penalva
Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Jeremy R. Sanford
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA
DOI
https://doi.org/10.1016/j.celrep.2016.04.083
Journal volume & issue
Vol. 15,
no. 9
Abstract
Read online
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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