The production of gametes in mammals is an elaborate process that begins during embryogenesis and continues during the reproductive life of the organism. Gametogenesis involves the production of highly specialized cells with unique organelles designed to accomplish the union of sperm and egg at fertilization. The timely production of developmental^ important products involves the regulated translation of mRNAs that have accumulated earlier during gametogenesis. Deviation from the wild-type timing of translation can cause cessation of gametogenesis and lead to sterility. The goals of this proposal are to further our understanding of the mechanisms of translational repression and activation during mammalian spermatogenesis. The studies in this proposal will focus on the regulation of posttranscriptional control in adult male germ line cells in mice.
In Aim 1, the function of the Y box proteins MSY2 and MSY4 will be investigated using conditional gene targeting.
In Aim 2, MSY2 and MSY4-interacting proteins will be identified by mass spectrometry analysis of ribonucleoprotein particles precipitated with MSY2 and MSY4 antibodies. Prm1-enriched mRNPs will be isolated using biotinylated antisense RNAs and streptavidin-coated immunomagnetic beads.
In Aim 3, proteins identified by mass spectrometry will be verified using complementary methods and functional studies will be pursued in cell culture and in vitro to determine how the associated proteins contribute to translational repression and mRNA stability. The knowledge gained from these studies may be useful in the genetic assessment of male infertility in humans, and lead to the development of male contraceptives designed to disrupt essential regulatory steps during normal spermatogenesis.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Cellular, Molecular and Integrative Reproduction Study Section (CMIR)
Program Officer
Moss, Stuart B
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Jackson Laboratory
Bar Harbor
United States
Zip Code
Snyder, Elizabeth; Soundararajan, Ramani; Sharma, Manju et al. (2015) Compound Heterozygosity for Y Box Proteins Causes Sterility Due to Loss of Translational Repression. PLoS Genet 11:e1005690
Greenlee, Anne R; Shiao, Meng-Shin; Snyder, Elizabeth et al. (2012) Deregulated sex chromosome gene expression with male germ cell-specific loss of Dicer1. PLoS One 7:e46359
Kaneko, Hiroki; Dridi, Sami; Tarallo, Valeria et al. (2011) DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature 471:325-30
Daher, Aicha; Laraki, Ghislaine; Singh, Madhurima et al. (2009) TRBP control of PACT-induced phosphorylation of protein kinase R is reversed by stress. Mol Cell Biol 29:254-65
Sadate-Ngatchou, Patricia I; Payne, Christopher J; Dearth, Andrea T et al. (2008) Cre recombinase activity specific to postnatal, premeiotic male germ cells in transgenic mice. Genesis 46:738-42
Connolly, Charles M; Dearth, Andrea T; Braun, Robert E (2005) Disruption of murine Tenr results in teratospermia and male infertility. Dev Biol 278:13-21
Giorgini, Flaviano; Davies, Holly G; Braun, Robert E (2002) Translational repression by MSY4 inhibits spermatid differentiation in mice. Development 129:3669-79
Zhong, J; Peters, A H; Kafer, K et al. (2001) A highly conserved sequence essential for translational repression of the protamine 1 messenger rna in murine spermatids. Biol Reprod 64:1784-9
Giorgini, F; Davies, H G; Braun, R E (2001) MSY2 and MSY4 bind a conserved sequence in the 3' untranslated region of protamine 1 mRNA in vitro and in vivo. Mol Cell Biol 21:7010-9
Nadler, J J; Braun, R E (2000) Fanconi anemia complementation group C is required for proliferation of murine primordial germ cells. Genesis 27:117-23

Showing the most recent 10 out of 22 publications