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Post-transcriptional Control and Male Infertility

  • Chapter
The Genetic Basis of Male Infertility

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 28))

Abstract

The importance of RNA binding proteins in male fertility is gaining great momentum. There are now several examples in humans and mice where mutations in genes encoding RNA binding proteins cause infertility. These include male-specific fertility factors that map to the Y chromosome, and autosomal genes whose functions are not restricted to the testis. In most cases the exact function of the RNA binding proteins is unknown, as are their in vivo RNA substrates. The need for post-transcriptional control during germ cell differentiation has also been demonstrated by studying specific mRNAs, principally the protamine mRNAs, whose temporal translational regulation in spermatids is essential for normal spermatogenesis. The search for message-specific RNA binding proteins has led to the discovery of several novel proteins that localize to different compartments in differentiating spermatogenic cells. Emerging genetic evidence suggests that these proteins have essential functions in developing germ cells.

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References

  • Aoki K, Suzuki K, Sugano T, Tasaka T, Nakahara K, Kuge O, Omori A, Kasai, M (1995) A novel gene, Translin, encodes a recombination hotspot binding protein associated with chromosomal translocations. Nat Genet 10: 167–174

    Google Scholar 

  • Balhorn R, Weston S, Thomas C, Wyrobek AJ (1984) DNA packaging in mouse spermatids. Synthesis of protamine variants and four transition proteins. Exp Cell Res 150: 298–308

    Google Scholar 

  • Balhorn R, Reed S, Tanphaichitr N (1988) Aberrant protamine 1/protamine 2 ratios in sperm of infertile human males. Experientia 44: 52–55

    Article  PubMed  CAS  Google Scholar 

  • Beck ARP, Miller IJ, Anderson P, Streuli M (1998) RNA-binding protein TIAR is essential for primordial germ cell development. Proc Natl Acad Sci USA 95: 2331–2336

    Article  PubMed  CAS  Google Scholar 

  • Bouvet P, Matsumoto K, Wolfe AP (1995) Sequence-specific RNA recognition by the Xeno-pus Y-box proteins. An essential role for the cold shock domain. J Biol Chem 270: 28 297–28 303

    Google Scholar 

  • Braun RE (1990) Temporal translational regulation of the protamine 1 gene during mouse spermatogenesis. Enzyme 44: 120–128

    PubMed  CAS  Google Scholar 

  • Braun RE, Behringer RR, Peschon JJ, Brinster RL, Palmiter RD (1989a) Genetically haploid spermatids are phenotypically diploid. Nature 337: 373–376

    Article  PubMed  CAS  Google Scholar 

  • Braun RE, Peschon JJ, Behringer RR, Brinster RL, Palmiter RD (1989b) Protamine 3’-untranslated sequences regulate temporal translational control and subcellular localization of growth hormone in spermatids of transgenic mice. Genes Dev 3: 793–802

    Article  PubMed  CAS  Google Scholar 

  • Burgos MH, Fawcett DW (1955) Studies on the fine structure of the mammalian testis. I. Differentiation of the spermatids in the cat (Felis domestica). J Biophys Biochem Cytol 1: 287–300

    Article  PubMed  CAS  Google Scholar 

  • Chevaillier P, Mauro N, Feneux D, Jouannet P, David G (1987) Anomalous protein complement of sperm nuclei in some infertile men [letter]. Lancet 2: 806–807

    Article  PubMed  CAS  Google Scholar 

  • Curtis D, Lehmann R, Zamore PD (1995) Translational regulation in development. Cell 81: 171–178

    Article  PubMed  CAS  Google Scholar 

  • Dadoune JP, Mayaux MJ, Guihard Moscato ML (1988) Correlation between defects in chromatin condensation of human spermatozoa stained by aniline blue and semen characteristics. Andrologia 20: 211–217

    Article  PubMed  CAS  Google Scholar 

  • de Yebra L, Ballesca JL, Vanrell JA, Bassas L, Oliva R (1993) Complete selective absence of protamine P2 in humans. J Biol Chem 268: 10553–10557

    PubMed  Google Scholar 

  • Eberhart CG, Wasserman SA (1995) The pelota locus encodes a protein required for meiotic cell division: an analysis of G2/M arrest in Drosophila spermatogenesis. Development 121: 3477–3486

    PubMed  CAS  Google Scholar 

  • Eberhart CG, Maines JZ, Wasserman SA (1996) Meiotic cell cycle requirement for a fly homologue of human Deleted in Azoospermia. Nature 381: 783–785

    Article  PubMed  CAS  Google Scholar 

  • Elliott DJ, Cooke HJ (1997) The molecular genetics of male infertility. Bioessays 19:801–809 Elliott DJ, Ma K, Kerr SM, Thakrar R, Speed R, Chandley AC, Cooke H (1996) An RBM homologue maps to the mouse Y chromosome and is expressed in germ cells. Hum Mol Genet 5: 869–874

    Article  Google Scholar 

  • Elliott DJ, Millar MR, Oghene K, Ross A, Kiesewetter F, Pryor J, McIntyre M, Hargreave TB, Saunders PT, Vogt PH, Chandley AC, Cooke H (1997) Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm. Proc Natl Acad Sci USA 94: 3848–3853

    Article  PubMed  CAS  Google Scholar 

  • Engh E, Clausen OP, Scholberg A, Tollefsrud A, Purvis K (1992) Relationship between sperm quality and chromatin condensation measured by sperm DNA fluorescence using flow cytometry. Int J Androl 15: 407–415

    Article  PubMed  CAS  Google Scholar 

  • Fajardo MA, Butner KA, Lee K, Braun RE (1994) Germ cell-specific proteins interact with the 3’ untranslated regions of Prm-1 and Prm-2 mRNA. Dev Biol 166: 643–653

    Article  PubMed  CAS  Google Scholar 

  • Fajardo MA, Haugen HS, Clegg CH, Braun RE (1997) Separate elements in the 3’ untranslated region of the mouse protamine 1 mRNA regulate translational repression and activation during murine spermatogenesis. Dev Biol 191: 42–52

    Article  PubMed  CAS  Google Scholar 

  • Fawcett DW, Anderson WA, Phillips DM (1971) Morphogenetic factors influencing the shape of the sperm head. Dev Biol 26: 220–251

    Article  PubMed  CAS  Google Scholar 

  • Foresta C, Zorzi M, Rossato M, Varotto A (1992) Sperm nuclear instability and staining with aniline blue: abnormal persistence of histones in spermatozoa in infertile men. Int J Androl 15: 330–337

    Article  PubMed  CAS  Google Scholar 

  • Geballe AP, Morris DR (1994) Initiation codons within 5’-leaders of mRNAs as regulators of translation. Trends Biochem Sci 19: 159–164

    Article  PubMed  CAS  Google Scholar 

  • Gold B, Fujimoto H, Kramer JM, Erickson RP, Hecht NB (1983) Haploid accumulation and translational control of phosphoglycerate kinase-2 messenger RNA during mouse spermatogenesis. Dev Biol 98: 392–399

    Article  PubMed  CAS  Google Scholar 

  • Green GR, Balhorn R, Poccia DL, Hecht NB (1994) Synthesis and processing of mammalian protamines and transition proteins. Mol Reprod Dev 37: 255–263

    Article  PubMed  CAS  Google Scholar 

  • Green SR, Mathews MB (1992) Two RNA-binding motifs in the double-stranded RNA-activated protein kinase, DAI. Genes Dev 6: 2478–2490

    Google Scholar 

  • Gu,W, Kwon Y, Oko R, Hermo L, Hecht NB (1995) Poly ( A) binding protein is bound to both stored and polysomal mRNAs in the mammalian testis. Mol Reprod Dev 40: 273–285

    Google Scholar 

  • Hecht NB (1989) Mammalian protamines and their expression. In: Hnilico G, Stein G, Stein J (eds) Histones and other basic nuclear proteins. CRC Press, Boca Raton

    Google Scholar 

  • Heidaran MA, Kistler WS (1987) Transcriptional and translational control of the message for transition protein 1, a major chromosomal protein of mammalian spermatids. J Biol Chem 262: 13309–13315

    PubMed  CAS  Google Scholar 

  • Heidaran MA, Showman RM, Kistler WS (1988) A cytochemical study of the transcriptional and translational regulation of nuclear transition protein 1 (TP1), a major chromosomal protein of mammalian spermatids. J Cell Biol 106: 1427–1433

    Article  PubMed  CAS  Google Scholar 

  • Hershey JW (1991) Translational control in mammalian cells. Annu Rev Biochem 60: 717–755

    Article  PubMed  CAS  Google Scholar 

  • Hesketh J (1994) Translation and the cytoskeleton: a mechanism for targeted protein synthesis. Mol Biol Rep 19: 233–243

    Article  PubMed  CAS  Google Scholar 

  • Johnson MD, Tho SP, Behzadian A, McDonough PG (1989) Molecular scanning of Yg11 (interval 6) in men with Sertoli-cell-only syndrome. Am J Obstet Gynecol 161: 1732–1737

    PubMed  CAS  Google Scholar 

  • Kierszenbaum AL, Tres IL (1975) Structural and transcriptional features of the mouse spermatid genome. J Cell Biol 65: 258–270

    Article  PubMed  CAS  Google Scholar 

  • Kleene KC (1989) Poly(A) shortening accompanies the activation of translation of five mRNAs during spermiogenesis in the mouse. Development 106: 367–373

    PubMed  CAS  Google Scholar 

  • Kleene KC (1996) Patterns of translational regulation in the mammalian testis. Mol Reprod Dev 43: 268–281

    Article  PubMed  CAS  Google Scholar 

  • Kleene KC, Distel RJ, Hecht NB (1984) Translational regulation and deadenylation of a protamine mRNA during spermiogenesis in the mouse. Dev Biol 105: 71–79

    Article  PubMed  CAS  Google Scholar 

  • Krawetz SA, Connor W, Dixon GH (1987) Cloning of bovine P1 protamine cDNA and the evolution of vertebrate P1 protamines. DNA 6: 47–57

    CAS  Google Scholar 

  • Kwon YK, Hecht NB (1991) Cytoplasmic protein binding to highly conserved sequences in the 3’ untranslated region of mouse protamine 2 mRNA, a translationally regulated transcript of male germ cells. Proc Natl Acad Sci USA 88: 3584–3588

    Article  PubMed  CAS  Google Scholar 

  • Kwon YK, Hecht NB (1993) Binding of a phosphoprotein to the 3’ untranslated region of the mouse protamine 2 mRNA temporally represses its translation. Mol Cell Biol 13: 6547–6557

    PubMed  CAS  Google Scholar 

  • Kwon YK, Murray MT, Hecht NB (1993) Proteins homologous to the Xenopus germ cell-specific RNA-binding proteins p54/p56 are temporally expressed in mouse male germ cells. Dev Biol 158: 99–100

    Article  PubMed  CAS  Google Scholar 

  • Lee CH, Hoyer FS, Engel W (1987) The nucleotide sequence of a human protamine 1 cDNA. Nucleic Acids Res 15: 7639

    Article  PubMed  CAS  Google Scholar 

  • Lee K, Haugen HS, Clegg CH, Braun RE (1995) Premature translation of protamine 1 mRNA causes precocious nuclear condensation and arrests spermatid differentiation in mice. Proc Natl Acad Sci USA 92: 12 451–12455

    Article  Google Scholar 

  • Lee K, Fajardo MA, Braun RE (1996) A testis cytoplasmic RNA-binding protein that has the properties of a translational repressor. Mol Cell Biol 16: 3023–3034

    PubMed  CAS  Google Scholar 

  • Ma K, Inglis JD, Sharkey A, Bickmore WA, Hill RE, Prosser EJ, Speed RM, Thomson EJ, Jobling M, Taylor K, et al (1993) A Y chromosome gene family with RNA-binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell 75: 1287–1295

    Article  PubMed  CAS  Google Scholar 

  • MacKinnon EA, Abraham JP (1972) The manchette in stage 14 rat spermatids: a possible structural relationship with the redundant nuclear envelope. Z Zellforsch Mikrosk Anat 124: 1–11

    PubMed  CAS  Google Scholar 

  • Mali P, Kaipia A, Kangasniemi M, Toppari J, Sandberg M, Hecht NB, Parvinen M (1989) Stage-specific expression of nucleoprotein mRNAs during rat and mouse spermiogenesis. Reprod Fertil Dev 1: 369–382

    Article  PubMed  CAS  Google Scholar 

  • McCarrey JR, Berg WM, Paragioudakis SJ, Zhang PL, Dilworth DD, Arnold BL, Rossi JJ (1992) Differential transcription of Pgk genes during spermatogenesis in the mouse. Dev Biol 154: 160–168

    Article  PubMed  CAS  Google Scholar 

  • Mertineit C, Yoder JA, Taketo T, Laird DW, Trasler JM, Bestor TH (1998) Sex-specific exons control DNA methyltransferase in mammalian germ cells. Development 125: 889–897

    PubMed  CAS  Google Scholar 

  • Monesi V (1964) Ribonucleic acid synthesis during mitosis and meiosis in the mouse testis. J Cell Biol 22: 521–532

    Article  PubMed  CAS  Google Scholar 

  • Morales CR, Kwon YK, Hecht NB (1991) Cytoplasmic localization during storage and translation of the mRNAs of transition protein 1 and protamine 1, two translationally regulated transcripts of the mammalian testis. J Cell Sci 100: 119–131

    PubMed  CAS  Google Scholar 

  • Murray MT, Krohne G, Franke WW (1991) Different forms of soluble cytoplasmic mRNA bind- ing proteins and particles in Xenopus laevis oocytes and embryos. J Cell Biol 112: 1–11

    Article  PubMed  CAS  Google Scholar 

  • Murray MT, Schiller DL, Franke WW (1992) Sequence analysis of cytoplasmic mRNA-binding proteins of Xenopus oocytes identifies a family of RNA-binding proteins. Proc Natl Acad Sci USA 89: 11–15

    Article  PubMed  CAS  Google Scholar 

  • Oko R, Korley R, Murray MT, Hecht NB, Hermo L (1996) Germ cell-specific DNA and RNA binding proteins p48/52 are expressed at specific stages of male germ cell development and are present in the chromatoid body. Mol Reprod Dev 44: 1–13

    Article  PubMed  CAS  Google Scholar 

  • Peschon JJ, Behringer RR, Brinster RL, Palmiter RD (1987) Spermatid-specific expression of protamine 1 in transgenic mice. Proc Natl Acad Sci USA 84: 5316–5319

    Article  PubMed  CAS  Google Scholar 

  • Reijo R, Lee TY, Salo P, Alagappan R, Brown LG, Rosenberg M, Rozen S, Jaffe T, Straus D, Hovatta 0, et al (1995) Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nat Genet 10: 383–393

    Article  PubMed  CAS  Google Scholar 

  • Reijo R, Alagappan RK, Patrizio P, Page DC (1996a) Severe oligozoospermia resulting from deletions of azoospermia factor gene on the Y chromosome [see comments]. Lancet 347: 1290–1293

    Article  PubMed  CAS  Google Scholar 

  • Reijo R, Seligman J, Dinulos MB, Jaffe T, Brown LG, Disteche CM, Page DC (1996b) Mouse autosomal homolog of DAZ, a candidate male sterility gene in humans, is expressed in male germ cells before and after puberty. Genomics 35: 346–352

    Article  PubMed  CAS  Google Scholar 

  • Richter JD, Evers DC (1984) A monoclonal antibody to an oocyte-specific poly(A) RNA-binding protein. J Biol Chem 259: 2190–2194

    PubMed  CAS  Google Scholar 

  • Robinson MO, Simon MI (1991) Determining transcript number using the polymerase chain reaction: Pgk-2, mP2, and Pgk-2 transgene mRNA levels during spermatogenesis. Nucleic Acids Res 19: 1557–1562

    Article  PubMed  CAS  Google Scholar 

  • Ruggiu M, Speed R, Taggart M, McKay SJ, Kilanowski F, Saunders P, Dorin J, Cooke HJ (1997) The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature 389: 73–77

    Article  PubMed  CAS  Google Scholar 

  • Russell L D, Russell JA, MacGregor GR, Meistrich ML (1991) Linkage of manchette microtubules to the nuclear envelope and observations of the role of the manchette in nuclear shaping during spermiogenesis in rodents. Am J Anat 192: 97–120

    Article  PubMed  CAS  Google Scholar 

  • Saxena R, Brown LG, Hawkins T, Alagappan RK, Skaletsky H, Reeve MP, Reijo R, Rozen S, Dinulos MB, Disteche CM, Page DC (1996) The DAZ gene cluster on the human Y chromosome arose from an autosomal gene that was transposed, repeatedly amplified and pruned. Nat Genet 14: 292–299

    Article  PubMed  CAS  Google Scholar 

  • Schlicker M, Schnulle V, Schneppel L, Vorob’ev VI, Engel W (1994) Disturbances of nuclear condensation in human spermatozoa: search for mutations in the genes for protamine 1, protamine 2 and transition protein 1. Hum Reprod 9: 2313–2317

    PubMed  CAS  Google Scholar 

  • Schlicker M, Reim K, Schluter G, Engel W (1997) Specific binding of a 47-kilodalton protein to the 3’ untranslated region of rat transition protein 2 messenger ribonucleic acid. Biol Reprod 56: 697–706

    Article  PubMed  CAS  Google Scholar 

  • Schumacher JM, Lee K, Edelhoff S, Braun RE (1995a) Distribution of Tenr, an RNA Binding Protein, in a Lattice-Like Network within the Spermatid Nucleus in the Mouse. Biol of Reprod 52: 1274–1283

    Article  CAS  Google Scholar 

  • Schumacher JM, Lee K, Edelhoff S, Braun RE (1995b) Spnr, a Murine RNA-Binding Protein that is Localized to Cytoplasmic Microtubules. J Cell Biol 129: 1023–1032

    Article  PubMed  CAS  Google Scholar 

  • Schumacher JM, Artzt K, Braun RE (1998) Spermatid perinuclear ribonucleic acid-binding protein binds microtubules in vitro and associates with abnormal manchettes in vivo in mice. Biol Reprod 59: 69–76

    Article  PubMed  CAS  Google Scholar 

  • Skare J, Drwinga H, Wyandt H, vanderSpek J, Troxler R, Milunsky A (1990) Interstitial deletion involving most of Yq. Am J Med Genet 36: 394–397

    Article  PubMed  CAS  Google Scholar 

  • St-Johnston D, Brown NH, Gall JG, Janesch M (1992) A conserved double-stranded RNA-binding domain. Proc Natl Acad Sci USA 89: 10979–10983

    Article  PubMed  CAS  Google Scholar 

  • Tafuri SR, Wolffe AP (1990) Xenopus Y-box transcription factors: Molecular cloning, functional analysis, and developmental regulation. Proc Natl Acad Sci USA 87: 9028–9032

    Google Scholar 

  • Tafuri SR, Familari M, Wolffe AP (1993) A mouse Y box protein, MSY1, is associated with paternal mRNA in spermatocytes. J Biol Chem 268: 12213–12220

    PubMed  CAS  Google Scholar 

  • Tarun SZ, Jr, Sachs AB (1995) A common function for mRNA 5’ and 3’ ends in translation initiation in yeast. Genes Dev 9: 2997–3007

    Article  PubMed  CAS  Google Scholar 

  • Tarun SZ, Jr, Sachs AB (1996) Association of the yeast poly(A) tail binding protein with translation initiation factor eIF-4G. Embo J 15: 7168–7177

    PubMed  CAS  Google Scholar 

  • Tiepolo L, Zuffardi 0 (1976) Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet 34: 119–124

    CAS  Google Scholar 

  • Vereb M, Agulnik AI, Houston JT, Lipschultz LI, Lamb DJ, Bishop CE (1997) Absence of DAZ gene mutations in cases of non-obstructed azoospermia. Mol Hum Reprod 3: 55–59

    Article  PubMed  CAS  Google Scholar 

  • Vogt PH, Edelmann A, Kirsch S, Henegariu 0, Hirschmann P, Kiesewetter F, Kohn FM, Schill WB, Farah S, Ramos C, Hartmann M, Hartschuh W, Meschede D, Behre HM, Castel A, Nieschlag E, Weidner W, Grone HJ, Jung A, Engel W, Haidl G (1996) Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yg11. Hum Mol Genet 5: 933–943

    Article  PubMed  CAS  Google Scholar 

  • Weighardt F, Biamonti G, Riva S (1996) The roles of heterogeneous nuclear ribonucleoproteins (hnRNP) in RNA metabolism. Bioessays 18: 747–756

    Article  PubMed  CAS  Google Scholar 

  • Wickens M, Anderson P, Jackson RJ (1997) Life and death in the cytoplasm: messages from the 3’ end. Curr Opin Genet Dev 7: 220–232

    Article  PubMed  CAS  Google Scholar 

  • Wolffe AP (1994) Structural and functional properties of the evolutionarily ancient Y-box family of nucleic acid binding proteins. Bioessays 16: 245–251

    Article  PubMed  CAS  Google Scholar 

  • Wu XQ, Gu W, Meng X, Hecht NB (1997) The RNA-binding protein, TB-RBP, is the mouse homologue of translin, a recombination protein associated with chromosomal translocations. Proc Natl Acad Sci USA 94: 5640–5645

    Google Scholar 

  • Yelick PC, Kwon YH, Flynn JF, Borzorgzadeh A, Kleene KC, Hecht NB (1989) Mouse transition protein 1 is translationally regulated during the postmeiotic stages of spermatogenesis. Mol Reprod Dev 1: 193–200

    Article  PubMed  CAS  Google Scholar 

  • Zhong J, Peters AHFM, Lee K, Braun RE (1999) A double-stranded RNA binding protein required for activation of repressed messages in mammalian germ cells. Nat Genet 22: 175–178

    Article  Google Scholar 

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  1. Department of Genetics, University of Washington, Box 35 73 60, 1959 NE Pacific, Seattle, Washington, 98195, USA

    Robert E. Braun

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  1. Immunogénétique Humaine, Institut Pasteur, 25 rue du Dr. Roux, 75724, Paris Cedex 15, France

    Ken McElreavey

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Braun, R.E. (2000). Post-transcriptional Control and Male Infertility. In: McElreavey, K. (eds) The Genetic Basis of Male Infertility. Results and Problems in Cell Differentiation, vol 28. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-48461-5_5

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  • DOI: https://doi.org/10.1007/978-3-540-48461-5_5

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