title: Sam68 regulates translation of target mRNAs in male germ cells, necessary for mouse spermatogenesis.
abstract: Sam68 is a KH-type RNA-binding protein involved in several steps of RNA metabolism with potential implications in cell differentiation and cancer. However, its physiological roles are still poorly understood. Herein, we show that Sam68(-/-) male mice are infertile and display several defects in spermatogenesis, demonstrating an essential role for Sam68 in male fertility. Sam68(-/-) mice produce few spermatozoa, which display dramatic motility defects and are unable to fertilize eggs. Expression of a subset of messenger mRNAs (mRNAs) is affected in the testis of knockout mice. Interestingly, Sam68 is associated with polyadenylated mRNAs in the cytoplasm during the meiotic divisions and in round spermatids, when it interacts with the translational machinery. We show that Sam68 is required for polysomal recruitment of specific mRNAs and for accumulation of the corresponding proteins in germ cells and in a heterologous system. These observations demonstrate a novel role for Sam68 in mRNA translation and highlight its essential requirement for the development of a functional male gamete.
authors.affiliation: Department of Public Health and Cell Biology, Section of Anatomy, University of Rome Tor Vergata, 00133 Rome, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Paronetto
authors.forename: Valeria
authors.initials: V
authors.lastname: Messina
authors.forename: Enrica
authors.initials: E
authors.lastname: Bianchi
authors.forename: Marco
authors.initials: M
authors.lastname: Barchi
authors.forename: Gillian
authors.initials: G
authors.lastname: Vogel
authors.forename: Costanzo
authors.initials: C
authors.lastname: Moretti
authors.forename: Fioretta
authors.initials: F
authors.lastname: Palombi
authors.forename: Mario
authors.initials: M
authors.lastname: Stefanini
authors.forename: Raffaele
authors.initials: R
authors.lastname: Geremia
authors.forename: Stéphane
authors.initials: S
authors.lastname: Richard
authors.forename: Claudio
authors.initials: C
authors.lastname: Sette
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000502:physiology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005854:Germ Cells / Q000166:cytology / Q000502:physiology*; D008297:Male; D008540:Meiosis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000166:cytology / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; C491467:PF20 protein, mouse; D012333:RNA, Messenger; C529672:Spy1 protein, mouse; C086844:Nedd1 protein, mouse