Sam68 regulates translation of target mRNAs in male germ cells, necessary for mouse spermatogenesis.
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.
Paronetto
Maria Paola
MP
Department of Public Health and Cell Biology, Section of Anatomy, University of Rome Tor Vergata, 00133 Rome, Italy.
Messina
Valeria
V
Bianchi
Enrica
E
Barchi
Marco
M
Vogel
Gillian
G
Moretti
Costanzo
C
Palombi
Fioretta
F
Stefanini
Mario
M
Geremia
Raffaele
R
Richard
Stéphane
S
Sette
Claudio
C
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
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; C491467:PF20 protein, mouse; D012333:RNA, Messenger; C529672:Spy1 protein, mouse; C086844:Nedd1 protein, mouse