title: IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC.
abstract: 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.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA; The Donnelly Centre, University of Toronto, Toronto, ON M5S 1A1, Canada.
authors.forename: Hanane
authors.initials: H
authors.lastname: Ennajdaoui
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Howard
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA; The Donnelly Centre, University of Toronto, Toronto, ON M5S 1A1, Canada.
authors.forename: Timothy
authors.initials: T
authors.lastname: Sterne-Weiler
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA; Department of Genetics, Stanford University, 3165 Porter Drive, Palo Alto, CA 94304, USA.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Jahanbani
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA.
authors.forename: Doyle J
authors.initials: DJ
authors.lastname: Coyne
authors.affiliation: Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Uren
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA.
authors.forename: Marija
authors.initials: M
authors.lastname: Dargyte
authors.affiliation: Center for Biomolecular Science and Engineering, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA.
authors.forename: Sol
authors.initials: S
authors.lastname: Katzman
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA.
authors.forename: Jolene M
authors.initials: JM
authors.lastname: Draper
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wallace
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA.
authors.forename: Oscar
authors.initials: O
authors.lastname: Cazarez
authors.affiliation: Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Burns
authors.affiliation: Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Qiao
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Hinck
authors.affiliation: Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
authors.affiliation: Bioo Scientific Corporation, 7500 Burleston Road, Austin, TX 78744, USA.
authors.forename: Masoud M
authors.initials: MM
authors.lastname: Toloue
authors.affiliation: The Donnelly Centre, University of Toronto, Toronto, ON M5S 1A1, Canada.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Blencowe
authors.affiliation: Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Luiz O F
authors.initials: LO
authors.lastname: Penalva
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA. Electronic address: jsanfor2@ucsc.edu.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Sanford
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D022001:Focal Adhesions / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000378:metabolism*
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; C498780:IGF2BP3 protein, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex