title: Galectin-3 is a non-classic RNA binding protein that stabilizes the mucin MUC4 mRNA in the cytoplasm of cancer cells.
abstract: Pancreatic cancer cells express high levels of MUC1, MUC4 and MUC16 mRNAs that encode membrane-bound mucins. These mRNAs share unusual features such as a long half-life. However, it remains unknown how mucin mRNA stability is regulated. Galectin-3 (Gal-3) is an endogenous lectin playing important biological functions in epithelial cells. Gal-3 is encoded by LGALS3 which is up-regulated in pancreatic cancer. Despite the absence of a RNA-recognition motif, Gal-3 interacts indirectly with pre-mRNAs in the nucleus and promotes constitutive splicing. However a broader role of Gal-3 in mRNA fate is unexplored. We report herein that Gal-3 increases MUC4 mRNA stability through an intermediate, hnRNP-L which binds to a conserved CA repeat element in the 3'UTR in a Gal-3 dependent manner and also controls Muc4 mRNA levels in epithelial tissues of Gal3-/-mice. Gal-3 interacts with hnRNP-L in the cytoplasm, especially during cell mitosis, but only partly associates with protein markers of P-Bodies or Stress Granules. By RNA-IP plus RNA-seq analysis and imaging, we demonstrate that Gal-3 binds to mature spliced MUC4 mRNA in the perinuclear region, probably in hnRNP-L-containing RNA granules. Our findings highlight a new role for Gal-3 as a non-classic RNA-binding protein that regulates MUC4 mRNA post-transcriptionally.
authors.affiliation: Univ. Lille, UMR-S 1172 - JPARC - Jean-Pierre Aubert Research Center, F-59000 Lille, France.|Inserm, UMR-S 1172, Team "Mucins, Epithelial Differentiation and Carcinogenesis", F-59000 Lille, France.|CHU Lille, Service de Biochimie « Hormonologie, Métabolisme-Nutrition, Oncologie », F-59000 Lille, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Coppin
authors.affiliation: Univ. Lille, UMR-S 1172 - JPARC - Jean-Pierre Aubert Research Center, F-59000 Lille, France.|Inserm, UMR-S 1172, Team "Mucins, Epithelial Differentiation and Carcinogenesis", F-59000 Lille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Vincent
authors.affiliation: Univ. Lille, RADEME (Research team on rare developmental and metabolic diseases), F-59000 Lille, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Frénois
authors.affiliation: Univ. Lille, UMR-S 1172 - JPARC - Jean-Pierre Aubert Research Center, F-59000 Lille, France.|Inserm, UMR-S 1172, Team "Mucins, Epithelial Differentiation and Carcinogenesis", F-59000 Lille, France.
authors.forename: Belinda
authors.initials: B
authors.lastname: Duchêne
authors.affiliation: Univ. Lille, UMR-S 1172 - JPARC - Jean-Pierre Aubert Research Center, F-59000 Lille, France.|Inserm, UMR-S 1172, Team "Mucins, Epithelial Differentiation and Carcinogenesis", F-59000 Lille, France.
authors.forename: Fatima
authors.initials: F
authors.lastname: Lahdaoui
authors.affiliation: CHU Lille, Service de Biochimie « Hormonologie, Métabolisme-Nutrition, Oncologie », F-59000 Lille, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Stechly
authors.affiliation: Univ. Lille, UMR-S 1172 - JPARC - Jean-Pierre Aubert Research Center, F-59000 Lille, France.|Inserm, UMR-S 1172, Team "Mucins, Epithelial Differentiation and Carcinogenesis", F-59000 Lille, France.|CHU Lille, Service d'anatomie-cytologie-pathologie, F-59000 Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Renaud
authors.affiliation: Univ. Lille, CHU Lille, Plate-forme de génomique fonctionnelle, Centre de Biologie et Pathologie, F-59037 Lille cedex, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Villenet
authors.affiliation: Univ. Lille, UMR-S 1172 - JPARC - Jean-Pierre Aubert Research Center, F-59000 Lille, France.|Inserm, UMR-S 1172, Team "Mucins, Epithelial Differentiation and Carcinogenesis", F-59000 Lille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van Seuningen
authors.affiliation: Univ. Lille, UMR-S 1172 - JPARC - Jean-Pierre Aubert Research Center, F-59000 Lille, France.|Inserm, UMR-S 1172, Team "Mucins, Epithelial Differentiation and Carcinogenesis", F-59000 Lille, France.|CHU Lille, Service d'anatomie-cytologie-pathologie, F-59000 Lille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leteurtre
authors.affiliation: Equipe Ingénierie Moléculaire et Glycobiologie, UMR CNRS 6286, Unité Fonctionnalité et Ingénierie des Protéines, Faculté des Sciences et Techniques, F-44322 Nantes cedex 3, France.
authors.forename: Johann
authors.initials: J
authors.lastname: Dion
authors.affiliation: Equipe Ingénierie Moléculaire et Glycobiologie, UMR CNRS 6286, Unité Fonctionnalité et Ingénierie des Protéines, Faculté des Sciences et Techniques, F-44322 Nantes cedex 3, France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Grandjean
authors.affiliation: Equipe « Morphogenèse, homéostasie et pathologies » Institut Jacques Monod - UMR 7592 CNRS - Université Paris Diderot, F-75205 Paris Cedex 13, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Poirier
authors.affiliation: Univ. Lille, CHU Lille, Plate-forme de génomique fonctionnelle, Centre de Biologie et Pathologie, F-59037 Lille cedex, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Figeac
authors.affiliation: Equipe CAM « Cell adhesion and mechanics" Institut Jacques Monod - UMR 7592 CNRS - Université Paris Diderot, F-75205 Paris Cedex 13, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Delacour
authors.affiliation: Univ. Lille, UMR-S 1172 - JPARC - Jean-Pierre Aubert Research Center, F-59000 Lille, France.|Inserm, UMR-S 1172, Team "Mucins, Epithelial Differentiation and Carcinogenesis", F-59000 Lille, France.|CHU Lille, Service de Biochimie « Hormonologie, Métabolisme-Nutrition, Oncologie », F-59000 Lille, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Porchet
authors.affiliation: Univ. Lille, UMR-S 1172 - JPARC - Jean-Pierre Aubert Research Center, F-59000 Lille, France.|Inserm, UMR-S 1172, Team "Mucins, Epithelial Differentiation and Carcinogenesis", F-59000 Lille, France.|CHU Lille, Service de Biochimie « Hormonologie, Métabolisme-Nutrition, Oncologie », F-59000 Lille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pigny
mesh_terms: D000818:Animals; D001798:Blood Proteins; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism*; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism*; D037502:Galectin 3 / Q000378:metabolism*; D037161:Galectins; D005786:Gene Expression Regulation; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055264:Mucin-4 / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human; C524658:MUC4 protein, human; D055264:Mucin-4; D012333:RNA, Messenger