title: BTG2 bridges PABPC1 RNA-binding domains and CAF1 deadenylase to control cell proliferation.
abstract: While BTG2 plays an important role in cellular differentiation and cancer, its precise molecular function remains unclear. BTG2 interacts with CAF1 deadenylase through its APRO domain, a defining feature of BTG/Tob factors. Our previous experiments revealed that expression of BTG2 promoted mRNA poly(A) tail shortening through an undefined mechanism. Here we report that the APRO domain of BTG2 interacts directly with the first RRM domain of the poly(A)-binding protein PABPC1. Moreover, PABPC1 RRM and BTG2 APRO domains are sufficient to stimulate CAF1 deadenylase activity in vitro in the absence of other CCR4-NOT complex subunits. Our results unravel thus the mechanism by which BTG2 stimulates mRNA deadenylation, demonstrating its direct role in poly(A) tail length control. Importantly, we also show that the interaction of BTG2 with the first RRM domain of PABPC1 is required for BTG2 to control cell proliferation.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France.|Centre National de la Recherche Scientifique UMR7104, 67404 Illkirch, France.|Institut National de la Santé et de la Recherche Médicale U964, 67404 Illkirch, France.|Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Stupfler
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France.|Centre National de la Recherche Scientifique UMR7104, 67404 Illkirch, France.|Institut National de la Santé et de la Recherche Médicale U964, 67404 Illkirch, France.|Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Birck
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France.|Centre National de la Recherche Scientifique UMR7104, 67404 Illkirch, France.|Institut National de la Santé et de la Recherche Médicale U964, 67404 Illkirch, France.|Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Séraphin
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France.|Centre National de la Recherche Scientifique UMR7104, 67404 Illkirch, France.|Institut National de la Santé et de la Recherche Médicale U964, 67404 Illkirch, France.|Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mauxion
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D057809:HEK293 Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D039122:Poly(A)-Binding Protein I / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C489780:CNOT8 protein, human; D017874:Immediate-Early Proteins; D039122:Poly(A)-Binding Protein I; D012333:RNA, Messenger; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070114:BTG2 protein, human