The long-term ojective of these studies is to understand how the synthesis of specific temporally expressed proteins is regulated in the mammalian testis. Emphasis will be placed upon establishing the function of a unique testicular a-tubulin and defining the cis-acting regulatory sequences in the genomic DNA of this tubulin and several other haploid gene products including the two protamines. Additional studies will explain how coordinate expression of genes in pre-meiotic, meiotic and post-meiotic testicular cells is controlled. Specific projects to be undertaken include: 1) determining the localization in testicular cells by immunofluorescence of the unique post-meiotically synthesized mouse a-tubulin. 2) determining whether a common DNA enhancer sequence regulates the synthesis of the protamine, a-tubulin, and other coordinately expressed haploid genes. 3) identifying specific cDNA and genomic clones for pre-meiotic and meiotic testicular cell-types to allow a direct comparison of genomic regulatory signals to be made between different classes of temporally regulated genes. 4) establishing the relationship between DNA methylation and the gene transcription and nuclear geome condensation with our growing collection of cell-type specific probes. These studies on the molecular basis for gene regulation in the testis will enhance our knowledge of basic control mechanisms during spermatagenesis, provide necessary probes to understand molecular causes of infertility, and provide superior approaches to fertility control.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD028832-13
Application #
3330374
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1980-09-01
Project End
1996-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
13
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Tufts University
Department
Type
Schools of Arts and Sciences
DUNS #
073134835
City
Medford
State
MA
Country
United States
Zip Code
02155
Xu, Mingang; McCarrey, John R; Hecht, Norman B (2008) A cytoplasmic variant of the KH-type splicing regulatory protein serves as a decay-promoting factor for phosphoglycerate kinase 2 mRNA in murine male germ cells. Nucleic Acids Res 36:7157-67
Yu, Zuoren; Hecht, Norman B (2008) The DNA/RNA-binding protein, translin, binds microRNA122a and increases its in vivo stability. J Androl 29:572-9
Xu, Mingang; Hecht, Norman B (2008) MSY2 and polypyrimidine tract binding protein 2 stabilize mRNAs in the mammalian testis. Int J Androl 31:457-61
Xu, Mingang; You, Yun; Hunsicker, Patricia et al. (2008) Mice deficient for a small cluster of Piwi-interacting RNAs implicate Piwi-interacting RNAs in transposon control. Biol Reprod 79:51-7
Iguchi, Naoko; Xu, Mingang; Hori, Tamaki et al. (2007) Noncoding RNAs of the mammalian testis: the meiotic transcripts Nct1 and Nct2 encode piRNAs. Ann N Y Acad Sci 1120:84-94
Xu, Mingang; Hecht, Norman B (2007) Polypyrimidine tract binding protein 2 stabilizes phosphoglycerate kinase 2 mRNA in murine male germ cells by binding to its 3'UTR. Biol Reprod 76:1025-33
Stein, Joel M; Bergman, Wayland; Fang, Yanshan et al. (2006) Behavioral and neurochemical alterations in mice lacking the RNA-binding protein translin. J Neurosci 26:2184-96
Iguchi, Naoko; Tobias, John W; Hecht, Norman B (2006) Expression profiling reveals meiotic male germ cell mRNAs that are translationally up- and down-regulated. Proc Natl Acad Sci U S A 103:7712-7
Yu, Zuoren; Raabe, Tobias; Hecht, Norman B (2005) MicroRNA Mirn122a reduces expression of the posttranscriptionally regulated germ cell transition protein 2 (Tnp2) messenger RNA (mRNA) by mRNA cleavage. Biol Reprod 73:427-33
Cho, Yoon Shin; Iguchi, Naoko; Yang, Juxiang et al. (2005) Meiotic messenger RNA and noncoding RNA targets of the RNA-binding protein Translin (TSN) in mouse testis. Biol Reprod 73:840-7

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