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

doi:10.1016/j.celrep.2016.04.083

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

Cell Systems & Anatomy

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1876-1883
Number of pages	8
Journal	Cell Reports
Volume	15
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2016.04.083
State	Published - May 31 2016

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2016.04.083

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Ennajdaoui, H., Howard, J. M., Sterne-Weiler, T., Jahanbani, F., Coyne, D. J., Uren, P. J., Dargyte, M., Katzman, S., Draper, J. M., Wallace, A., Cazarez, O., Burns, S. C., Qiao, M., Hinck, L., Smith, A. D., Toloue, M. M., Blencowe, B. J., Penalva, L. O. F., & Sanford, J. R. (2016). IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC. Cell Reports, 15(9), 1876-1883. https://doi.org/10.1016/j.celrep.2016.04.083

Ennajdaoui, H, Howard, JM, Sterne-Weiler, T, Jahanbani, F, Coyne, DJ, Uren, PJ, Dargyte, M, Katzman, S, Draper, JM, Wallace, A, Cazarez, O, Burns, SC, Qiao, M, Hinck, L, Smith, AD, Toloue, MM, Blencowe, BJ, Penalva, LOF & Sanford, JR 2016, 'IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC', Cell Reports, vol. 15, no. 9, pp. 1876-1883. https://doi.org/10.1016/j.celrep.2016.04.083

@article{96a47b6d4cd3410d8ce90eeac4a7496c,

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.",

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

note = "Funding Information: This work was funded by the National Institutes of Health (NIH) through grants GM109146 (to J.R.S.), HG007336 (to M.M.T.), and HG006015 (to A.D.S. and L.O.F.P.); the Santa Cruz Cancer Benefit Group (to J.R.S.); the University of California Cancer Research Coordinating Committee (to J.R.S.) and CIRM grant TG2-00157 (to H.E.); CIRM Major Facilities grant FA1-00617-1; and CIRM Shared Stem Cell Facilities grant CL1-00506-1.2. T.S.-W. was supported in part by an operating grant from the Canadian Institutes of Health Research and a CH Best Foundation Postdoctoral Fellowship. We thank The Genome Sequencing and Analysis Facility at the University of Texas at Austin. Publisher Copyright: {\textcopyright} 2016 The Author(s).",

year = "2016",

month = may,

day = "31",

doi = "10.1016/j.celrep.2016.04.083",

language = "English (US)",

volume = "15",

pages = "1876--1883",

journal = "Cell Reports",

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number = "9",

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T1 - IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC

AU - Ennajdaoui, Hanane

AU - Howard, Jonathan M.

AU - Sterne-Weiler, Timothy

AU - Jahanbani, Fereshteh

AU - Coyne, Doyle J.

AU - Uren, Philip J.

AU - Dargyte, Marija

AU - Katzman, Sol

AU - Draper, Jolene M.

AU - Wallace, Andrew

AU - Cazarez, Oscar

AU - Burns, Suzanne C.

AU - Qiao, Mei

AU - Hinck, Lindsay

AU - Smith, Andrew D.

AU - Toloue, Masoud M.

AU - Blencowe, Benjamin J.

AU - Penalva, Luiz O.F.

AU - Sanford, Jeremy R.

N1 - Funding Information: This work was funded by the National Institutes of Health (NIH) through grants GM109146 (to J.R.S.), HG007336 (to M.M.T.), and HG006015 (to A.D.S. and L.O.F.P.); the Santa Cruz Cancer Benefit Group (to J.R.S.); the University of California Cancer Research Coordinating Committee (to J.R.S.) and CIRM grant TG2-00157 (to H.E.); CIRM Major Facilities grant FA1-00617-1; and CIRM Shared Stem Cell Facilities grant CL1-00506-1.2. T.S.-W. was supported in part by an operating grant from the Canadian Institutes of Health Research and a CH Best Foundation Postdoctoral Fellowship. We thank The Genome Sequencing and Analysis Facility at the University of Texas at Austin. Publisher Copyright: © 2016 The Author(s).

PY - 2016/5/31

Y1 - 2016/5/31

N2 - 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.

AB - 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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JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 9

ER -

IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC

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