title: The RNA Binding Protein IMP2 Preserves Glioblastoma Stem Cells by Preventing let-7 Target Gene Silencing.
abstract: Cancer stem cells (CSCs) can drive tumor growth, and their maintenance may rely on post-transcriptional regulation of gene expression, including that mediated by microRNAs (miRNAs). The let-7 miRNA family has been shown to induce differentiation by silencing stem cell programs. Let-7-mediated target gene suppression is prevented by LIN28A/B, which reduce let-7 biogenesis in normal embryonic and some cancer stem cells and ensure maintenance of stemness. Here, we find that glioblastoma stem cells (GSCs) lack LIN28 and express both let-7 and their target genes, suggesting LIN28-independent protection from let-7 silencing. Using photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP), we show that insulin-like growth factor 2 mRNA-binding protein 2 (IMP2) binds to let-7 miRNA recognition elements (MREs) and prevents let-7 target gene silencing. Our observations define the RNA-binding repertoire of IMP2 and identify a mechanism whereby it supports GSC and neural stem cell specification.
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, CHUV, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 25, 1011 Lausanne, Switzerland.
authors.forename: Nils
authors.initials: N
authors.lastname: Degrauwe
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Tommy B
authors.initials: TB
authors.lastname: Schlumpf
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Michalina
authors.initials: M
authors.lastname: Janiszewska
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, CHUV, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 25, 1011 Lausanne, Switzerland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Martin
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, CHUV, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 25, 1011 Lausanne, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Cauderay
authors.affiliation: Department of Molecular Biotechnology and Life Sciences, University of Turin, Turin 10126, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Provero
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, CHUV, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 25, 1011 Lausanne, Switzerland.
authors.forename: Nicolo
authors.initials: N
authors.lastname: Riggi
authors.affiliation: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Mario-L
authors.initials: ML
authors.lastname: Suvà
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Renato
authors.initials: R
authors.lastname: Paro
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, CHUV, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 25, 1011 Lausanne, Switzerland. Electronic address: ivan.stamenkovic@chuv.ch.
authors.forename: Ivan
authors.initials: I
authors.lastname: Stamenkovic
mesh_terms: D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D058953:Neural Stem Cells / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000473:pathology
chemical_list: C498779:IGF2BP2 protein, human; C516326:LIN28B protein, human; D035683:MicroRNAs; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human