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J. Cell Biol. 185 (2): 235-249

Copyright © 2009 by the Rockefeller University Press.

Article

Sam68 regulates translation of target mRNAs in male germ cells, necessary for mouse spermatogenesis

Maria Paola Paronetto1,3, Valeria Messina1,3, Enrica Bianchi1,3, Marco Barchi1, Gillian Vogel5,6,7, Costanzo Moretti2, Fioretta Palombi4, Mario Stefanini4, Raffaele Geremia1, Stéphane Richard5,6,7, , and Claudio Sette1,3

1 Department of Public Health and Cell Biology, Section of Anatomy, and 2 Department of Internal Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
3 Laboratory of Neuroembryology, Fondazione Santa Lucia, 00143 Rome, Italy
4 Department of Histology and Medical Embryology, Università di Roma La Sapienza, 00110 Rome, Italy
5 Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, 6 Department of Oncology, and 7 Department of Medicine, McGill University, Montréal, Québec, Canada, H3T1E2

Correspondence to Claudio Sette: claudio.sette{at}uniroma2.it; or Stéphane Richard: Stephane.Richard{at}mcgill.ca

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.

Maria Paola Paronetto's present address is Centre de Regulaciò Genomica, Barcelona 08003, Spain.

Abbreviations used in this paper: ANOVA, analysis of variance; dpp, days postpartum; ERK, extracellular signal-regulated kinase; IPA, Ingenuity Pathway Analysis; OA, okadaic acid; RBP, RNA-binding protein; RNP, ribonucleoprotein; STAR, signal transduction and activation of RNA; UTR, untranslated region.

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