The Chromatoid Body: A Specialized RNA Granule of Male Germ Cells

  • Ippei Nagamori
  • Adam Cruickshank
  • Paolo Sassone-Corsi
Chapter
Part of the Epigenetics and Human Health book series (EHH)

Abstract

RNA processing and miRNA pathways have been shown to exert a central control on a wide variety of cellular functions. The epigenetic program of male germ cells is highly specialized, including RNA processing pathways, which play an important role in the male germ cell lineage. Male germ cells differentiate through a remarkable process of cellular restructuring. One highly specialized structure is the chromatoid body (CB), a male reproductive cell-specific organelle that appears in spermatocytes and spermatids. It is a finely filamentous, lobulated perinuclear granule located in the cytoplasm of male germ cells. The molecular composition and function of the chromatoid body have remained elusive for a longtime. Accumulating evidence indicates that the CB is involved in RNA storing and metabolism, being related to the RNA processing body (P-body) of somatic cells. We propose that the CB operates as an intracellular nerve-center of the microRNA pathway. The role of the chromatoid body underscores the importance of posttranscriptional gene regulation and of the microRNA pathway in the control of postmeiotic male germ cell differentiation.

Keywords

Chromatoid body Epigenetics micro RNA Post-transcriptional regulation Spermatogenesis VASA 

References

  1. Anderson P, Kedersha N (2006) RNA granules. J Cell Biol 172(6):803–808PubMedCrossRefGoogle Scholar
  2. Anderson P, Kedersha N (2009) RNA granules: post-transcriptional and epigenetic modulators of gene expression. Nat Rev Mol Cell Biol 10(6):430–436PubMedCrossRefGoogle Scholar
  3. Andonov MD, Chaldakov GN (1989) Morphological evidence for calcium storage in the chromatoid body of rat spermatids. Experientia 45(4):377–378PubMedCrossRefGoogle Scholar
  4. Anton E (1983) Association of Golgi vesicles containing acid phosphatase with the chromatoid body of rat spermatids. Experientia 39(4):393–394PubMedCrossRefGoogle Scholar
  5. Aravin A, Gaidatzis D et al (2006) A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442(7099):203–207PubMedGoogle Scholar
  6. Aravin AA, Sachidanandam R et al (2007) Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316(5825):744–747PubMedCrossRefGoogle Scholar
  7. Bardsley A, McDonald K et al (1993) Distribution of tudor protein in the Drosophila embryo suggests separation of functions based on site of localization. Development 119(1):207–219PubMedGoogle Scholar
  8. Biggiogera M, Fakan S et al (1990) Immunoelectron microscopical visualization of ribonucleoproteins in the chromatoid body of mouse spermatids. Mol Reprod Dev 26(2):150–158PubMedCrossRefGoogle Scholar
  9. Braun RE (1998) Post-transcriptional control of gene expression during spermatogenesis. Semin Cell Dev Biol 9(4):483–489PubMedCrossRefGoogle Scholar
  10. Brengues M, Teixeira D et al (2005) Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies. Science 310(5747):486–489PubMedCrossRefGoogle Scholar
  11. Carmell MA, Xuan Z et al (2002) The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev 16(21):2733–2742PubMedCrossRefGoogle Scholar
  12. Carmell MA, Girard A et al (2007) MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev Cell 12(4):503–514PubMedCrossRefGoogle Scholar
  13. Chen C, Jin J et al (2009) Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi. Proc Natl Acad Sci USA 106(48):20336–20341PubMedCrossRefGoogle Scholar
  14. Chennathukuzhi V, Morales CR et al (2003a) The kinesin KIF17b and RNA-binding protein TB-RBP transport specific cAMP-responsive element modulator-regulated mRNAs in male germ cells. Proc Natl Acad Sci USA 100(26):15566–15571PubMedCrossRefGoogle Scholar
  15. Chennathukuzhi V, Stein JM et al (2003b) Mice deficient for testis-brain RNA-binding protein exhibit a coordinate loss of TRAX, reduced fertility, altered gene expression in the brain, and behavioral changes. Mol Cell Biol 23(18):6419–6434PubMedCrossRefGoogle Scholar
  16. Chuma S, Hiyoshi M et al (2003) Mouse Tudor Repeat-1 (MTR-1) is a novel component of chromatoid bodies/nuages in male germ cells and forms a complex with snRNPs. Mech Dev 120(9):979–990PubMedCrossRefGoogle Scholar
  17. Chuma S, Hosokawa M et al (2006) Tdrd1/Mtr-1, a tudor-related gene, is essential for male germ-cell differentiation and nuage/germinal granule formation in mice. Proc Natl Acad Sci USA 103(43):15894–15899PubMedCrossRefGoogle Scholar
  18. Coller J, Parker R (2005) General translational repression by activators of mRNA decapping. Cell 122(6):875–886PubMedCrossRefGoogle Scholar
  19. Costa Y, Speed RM et al (2006) Mouse MAELSTROM: the link between meiotic silencing of unsynapsed chromatin and microRNA pathway? Hum Mol Genet 15(15):2324–2334PubMedCrossRefGoogle Scholar
  20. Cougot N, Babajko S et al (2004) Cytoplasmic foci are sites of mRNA decay in human cells. J Cell Biol 165(1):31–40PubMedCrossRefGoogle Scholar
  21. Deng W, Lin H (2002) Miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis. Dev Cell 2(6):819–830PubMedCrossRefGoogle Scholar
  22. Eddy EM, O’Brien DA (1998) Gene expression during mammalian meiosis. Curr Top Dev Biol 37:141–200PubMedCrossRefGoogle Scholar
  23. Eulalio A, Behm-Ansmant I et al (2007) P bodies: at the crossroads of post-transcriptional pathways. Nat Rev Mol Cell Biol 8(1):9–22PubMedCrossRefGoogle Scholar
  24. Ewing LL, Davis JC et al (1980) Regulation of testicular function: a spatial and temporal view. Int Rev Physiol 22:41–115PubMedGoogle Scholar
  25. Fawcett DW, Eddy EM et al (1970) Observations on the fine structure and relationships of the chromatoid body in mammalian spermatogenesis. Biol Reprod 2(1):129–153PubMedCrossRefGoogle Scholar
  26. Fimia GM, De Cesare D et al (1999) CBP-independent activation of CREM and CREB by the LIM-only protein ACT. Nature 398(6723):165–169PubMedCrossRefGoogle Scholar
  27. Foulkes NS, Schlotter F et al (1993) Pituitary hormone FSH directs the CREM functional switch during spermatogenesis. Nature 362(6417):264–267PubMedCrossRefGoogle Scholar
  28. Fujiwara Y, Komiya T et al (1994) Isolation of a DEAD-family protein gene that encodes a murine homolog of Drosophila vasa and its specific expression in germ cell lineage. Proc Natl Acad Sci USA 91(25):12258–12262PubMedCrossRefGoogle Scholar
  29. Girard A, Sachidanandam R et al (2006) A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442(7099):199–202PubMedGoogle Scholar
  30. Golumbeski GS, Bardsley A et al (1991) Tudor, a posterior-group gene of Drosophila melanogaster, encodes a novel protein and an mRNA localized during mid-oogenesis. Genes Dev 5(11):2060–2070PubMedCrossRefGoogle Scholar
  31. Grivna ST, Beyret E et al (2006a) A novel class of small RNAs in mouse spermatogenic cells. Genes Dev 20(13):1709–1714PubMedCrossRefGoogle Scholar
  32. Grivna ST, Pyhtila B et al (2006b) MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis. Proc Natl Acad Sci USA 103(36):13415–13420PubMedCrossRefGoogle Scholar
  33. Haase AD, Jaskiewicz L et al (2005) TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing. EMBO Rep 6(10):961–967PubMedCrossRefGoogle Scholar
  34. Haley B, Zamore PD (2004) Kinetic analysis of the RNAi enzyme complex. Nat Struct Mol Biol 11(7):599–606PubMedCrossRefGoogle Scholar
  35. Haraguchi CM, Mabuchi T et al (2005) Chromatoid bodies: aggresome-like characteristics and degradation sites for organelles of spermiogenic cells. J Histochem Cytochem 53(4):455–465PubMedCrossRefGoogle Scholar
  36. Head JR, Kresge CK (1985) Reaction of the chromatoid body with a monoclonal antibody to a rat histocompatibility antigen. Biol Reprod 33(4):1001–1008PubMedCrossRefGoogle Scholar
  37. Hecht NB (1998) Molecular mechanisms of male germ cell differentiation. Bioessays 20(7):555–561PubMedCrossRefGoogle Scholar
  38. Hess RA, Miller LA et al (1993) Immunoelectron microscopic localization of testicular and somatic cytochromes c in the seminiferous epithelium of the rat. Biol Reprod 48(6):1299–1308PubMedCrossRefGoogle Scholar
  39. Hosokawa M, Shoji M et al (2007) Tudor-related proteins TDRD1/MTR-1, TDRD6 and TDRD7/TRAP: domain composition, intracellular localization, and function in male germ cells in mice. Dev Biol 301(1):38–52PubMedCrossRefGoogle Scholar
  40. Jankowsky E, Bowers H (2006) Remodeling of ribonucleoprotein complexes with DExH/D RNA helicases. Nucleic Acids Res 34(15):4181–4188PubMedCrossRefGoogle Scholar
  41. Kashiwabara S, Noguchi J et al (2002) Regulation of spermatogenesis by testis-specific, cytoplasmic poly(A) polymerase TPAP. Science 298(5600):1999–2002PubMedCrossRefGoogle Scholar
  42. Kedersha N, Stoecklin G et al (2005) Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. J Cell Biol 169(6):871–884PubMedCrossRefGoogle Scholar
  43. Kimmins S, Sassone-Corsi P (2005) Chromatin remodelling and epigenetic features of germ cells. Nature 434(7033):583–589PubMedCrossRefGoogle Scholar
  44. Kleene KC (1993) Multiple controls over the efficiency of translation of the mRNAs encoding transition proteins, protamines, and the mitochondrial capsule selenoprotein in late spermatids in mice. Dev Biol 159(2):720–731PubMedCrossRefGoogle Scholar
  45. Kojima K, Kuramochi-Miyagawa S et al (2009) Associations between PIWI proteins and TDRD1/MTR-1 are critical for integrated subcellular localization in murine male germ cells. Genes Cells 14(10):1155–1165PubMedCrossRefGoogle Scholar
  46. Kotaja N, Sassone-Corsi P (2007) The chromatoid body: a germ-cell-specific RNA-processing centre. Nat Rev Mol Cell Biol 8(1):85–90PubMedCrossRefGoogle Scholar
  47. Kotaja N, De Cesare D et al (2004) Abnormal sperm in mice with targeted deletion of the act (activator of cAMP-responsive element modulator in testis) gene. Proc Natl Acad Sci USA 101(29):10620–10625PubMedCrossRefGoogle Scholar
  48. Kotaja N, Macho B et al (2005) Microtubule-independent and protein kinase A-mediated function of kinesin KIF17b controls the intracellular transport of activator of CREM in testis (ACT). J Biol Chem 280(36):31739–31745PubMedCrossRefGoogle Scholar
  49. Kotaja N, Bhattacharyya SN et al (2006a) The chromatoid body of male germ cells: similarity with processing bodies and presence of Dicer and microRNA pathway components. Proc Natl Acad Sci USA 103(8):2647–2652PubMedCrossRefGoogle Scholar
  50. Kotaja N, Lin H et al (2006b) Interplay of PIWI/Argonaute protein MIWI and kinesin KIF17b in chromatoid bodies of male germ cells. J Cell Sci 119(Pt 13):2819–2825PubMedCrossRefGoogle Scholar
  51. Krimer DB, Esponda P (1980) Presence of polysaccharides and proteins in the chromatoid body of mouse spermatids. Cell Biol Int Rep 4(3):265–270PubMedCrossRefGoogle Scholar
  52. Kuramochi-Miyagawa S, Kimura T et al (2004) Mili, a mammalian member of piwi family gene, is essential for spermatogenesis. Development 131(4):839–849PubMedCrossRefGoogle Scholar
  53. Kuramochi-Miyagawa S, Watanabe T et al (2008) DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev 22(7):908–917PubMedCrossRefGoogle Scholar
  54. Lau NC, Seto AG et al (2006) Characterization of the piRNA complex from rat testes. Science 313(5785):363–367PubMedCrossRefGoogle Scholar
  55. Lee K, Haugen HS et al (1995) Premature translation of protamine 1 mRNA causes precocious nuclear condensation and arrests spermatid differentiation in mice. Proc Natl Acad Sci USA 92(26):12451–12455PubMedCrossRefGoogle Scholar
  56. Liang L, Diehl-Jones W et al (1994) Localization of vasa protein to the Drosophila pole plasm is independent of its RNA-binding and helicase activities. Development 120(5):1201–1211PubMedGoogle Scholar
  57. Liu J, Carmell MA et al (2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science 305(5689):1437–1441PubMedCrossRefGoogle Scholar
  58. Liu J, Rivas FV et al (2005a) A role for the P-body component GW182 in microRNA function. Nat Cell Biol 7(12):1261–1266PubMedCrossRefGoogle Scholar
  59. Liu J, Valencia-Sanchez MA et al (2005b) MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol 7(7):719–723PubMedCrossRefGoogle Scholar
  60. Macho B, Brancorsini S et al (2002) CREM-dependent transcription in male germ cells controlled by a kinesin. Science 298(5602):2388–2390PubMedCrossRefGoogle Scholar
  61. Meister G, Landthaler M et al (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15(2):185–197PubMedCrossRefGoogle Scholar
  62. Morales CR, Lefrancois S et al (2002) A TB-RBP and Ter ATPase complex accompanies specific mRNAs from nuclei through the nuclear pores and into intercellular bridges in mouse male germ cells. Dev Biol 246(2):480–494PubMedCrossRefGoogle Scholar
  63. Moussa F, Oko R et al (1994) The immunolocalization of small nuclear ribonucleoprotein particles in testicular cells during the cycle of the seminiferous epithelium of the adult rat. Cell Tissue Res 278(2):363–378PubMedCrossRefGoogle Scholar
  64. Nantel F, Monaco L et al (1996) Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice. Nature 380(6570):159–162PubMedCrossRefGoogle Scholar
  65. O’Donnell KA, Boeke JD (2007) Mighty Piwis defend the germline against genome intruders. Cell 129(1):37–44PubMedCrossRefGoogle Scholar
  66. Oakberg EF (1956) Duration of spermatogenesis in the mouse and timing of stages of the cycle of the seminiferous epithelium. Am J Anat 99(3):507–516PubMedCrossRefGoogle Scholar
  67. Olsen LC, Aasland R et al (1997) A vasa-like gene in zebrafish identifies putative primordial germ cells. Mech Dev 66(1–2):95–105PubMedCrossRefGoogle Scholar
  68. Paniagua R, Nistal M et al (1985) Presence of ribonucleoproteins and basic proteins in the nuage and intermitochondrial bars of human spermatogonia. J Anat 143:201–206PubMedGoogle Scholar
  69. Paronetto MP, Messina V et al (2009) Sam68 regulates translation of target mRNAs in male germ cells, necessary for mouse spermatogenesis. J Cell Biol 185(2):235–249PubMedCrossRefGoogle Scholar
  70. Parvinen M (2005) The chromatoid body in spermatogenesis. Int J Androl 28(4):189–201PubMedCrossRefGoogle Scholar
  71. Parvinen M, Parvinen LM (1979) Active movements of the chromatoid body. A possible transport mechanism for haploid gene products. J Cell Biol 80(3):621–628PubMedCrossRefGoogle Scholar
  72. Parvinen M, Kotaja N, Mishra DP, Sassone-Corsi P (2007) The chromatoid body and microRNA pathways in male germ cells. In: The genetics of male infertility. pp 199–209Google Scholar
  73. Pillai RS, Bhattacharyya SN et al (2005) Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 309(5740):1573–1576PubMedCrossRefGoogle Scholar
  74. Raz E (2000) The function and regulation of vasa-like genes in germ-cell development. Genome Biol 1(3):reviews1017.1–reviews1017.6CrossRefGoogle Scholar
  75. Reuter M, Chuma S et al (2009) Loss of the Mili-interacting Tudor domain-containing protein-1 activates transposons and alters the Mili-associated small RNA profile. Nat Struct Mol Biol 16(6):639–646PubMedCrossRefGoogle Scholar
  76. Rossi JJ (2005) RNAi and the P-body connection. Nat Cell Biol 7(7):643–644PubMedCrossRefGoogle Scholar
  77. Rouelle-Rossier VB, Biggiogera M et al (1993) Ultrastructural detection of calcium and magnesium in the chromatoid body of mouse spermatids by electron spectroscopic imaging and electron energy loss spectroscopy. J Histochem Cytochem 41(8):1155–1162PubMedCrossRefGoogle Scholar
  78. Sasaki T, Shiohama A et al (2003) Identification of eight members of the Argonaute family in the human genome small star, filled. Genomics 82(3):323–330PubMedCrossRefGoogle Scholar
  79. Sassone-Corsi P (1997) Transcriptional checkpoints determining the fate of male germ cells. Cell 88(2):163–166PubMedCrossRefGoogle Scholar
  80. Sassone-Corsi P (2002) Unique chromatin remodeling and transcriptional regulation in spermatogenesis. Science 296(5576):2176–2178PubMedCrossRefGoogle Scholar
  81. Saunders PT, Millar MR et al (1992) Stage-specific expression of rat transition protein 2 mRNA and possible localization to the chromatoid body of step 7 spermatids by in situ hybridization using a nonradioactive riboprobe. Mol Reprod Dev 33(4):385–391PubMedCrossRefGoogle Scholar
  82. Sen GL, Blau HM (2005) Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies. Nat Cell Biol 7(6):633–636PubMedCrossRefGoogle Scholar
  83. Seydoux G, Braun RE (2006) Pathway to totipotency: lessons from germ cells. Cell 127(5):891–904PubMedCrossRefGoogle Scholar
  84. Sheth U, Parker R (2003) Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science 300(5620):805–808PubMedCrossRefGoogle Scholar
  85. Shibata N, Tsunekawa N et al (2004) Mouse RanBPM is a partner gene to a germline specific RNA helicase, mouse vasa homolog protein. Mol Reprod Dev 67(1):1–7PubMedCrossRefGoogle Scholar
  86. Soderstrom KO, Parvinen M (1976) Incorporation of (3H)uridine by the chromatoid body during rat spermatogenesis. J Cell Biol 70(1):239–246PubMedCrossRefGoogle Scholar
  87. Sontheimer EJ (2005) Assembly and function of RNA silencing complexes. Nat Rev Mol Cell Biol 6(2):127–138PubMedCrossRefGoogle Scholar
  88. Styhler S, Nakamura A et al (1998) vasa is required for GURKEN accumulation in the oocyte, and is involved in oocyte differentiation and germline cyst development. Development 125(9):1569–1578PubMedGoogle Scholar
  89. Tanaka SS, Toyooka Y et al (2000) The mouse homolog of Drosophila Vasa is required for the development of male germ cells. Genes Dev 14(7):841–853PubMedGoogle Scholar
  90. Tang XM, Lalli MF et al (1982) A cytochemical study of the Golgi apparatus of the spermatid during spermiogenesis in the rat. Am J Anat 163(4):283–294PubMedCrossRefGoogle Scholar
  91. Teixeira D, Sheth U et al (2005) Processing bodies require RNA for assembly and contain nontranslating mRNAs. RNA 11(4):371–382PubMedCrossRefGoogle Scholar
  92. Thorne-Tjomsland G, Clermont Y et al (1988) Contribution of the Golgi apparatus components to the formation of the acrosomic system and chromatoid body in rat spermatids. Anat Rec 221(2):591–598PubMedCrossRefGoogle Scholar
  93. Toyooka Y, Tsunekawa N et al (2000) Expression and intracellular localization of mouse Vasa-homologue protein during germ cell development. Mech Dev 93(1–2):139–149PubMedCrossRefGoogle Scholar
  94. Tsai-Morris CH, Sheng Y et al (2004) Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is essential for spermatid development and completion of spermatogenesis. Proc Natl Acad Sci USA 101(17):6373–6378PubMedCrossRefGoogle Scholar
  95. Unhavaithaya Y, Hao Y et al (2009) MILI, a PIWI-interacting RNA-binding protein, is required for germ line stem cell self-renewal and appears to positively regulate translation. J Biol Chem 284(10):6507–6519PubMedCrossRefGoogle Scholar
  96. Vagin VV, Wohlschlegel J et al (2009) Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members. Genes Dev 23(15):1749–1762PubMedCrossRefGoogle Scholar
  97. Vasileva A, Tiedau D et al (2009) Tdrd6 is required for spermiogenesis, chromatoid body architecture, and regulation of miRNA expression. Curr Biol 19(8):630–639PubMedCrossRefGoogle Scholar
  98. Ventela S, Toppari J et al (2003) Intercellular organelle traffic through cytoplasmic bridges in early spermatids of the rat: mechanisms of haploid gene product sharing. Mol Biol Cell 14(7):2768–2780PubMedCrossRefGoogle Scholar
  99. Walt H, Armbruster BL (1984) Actin and RNA are components of the chromatoid bodies in spermatids of the rat. Cell Tissue Res 236(2):487–490PubMedCrossRefGoogle Scholar
  100. Wang J, Saxe JP et al (2009) Mili interacts with tudor domain-containing protein 1 in regulating spermatogenesis. Curr Biol 19(8):640–644PubMedCrossRefGoogle Scholar
  101. Watanabe T, Takeda A et al (2006) Identification and characterization of two novel classes of small RNAs in the mouse germline: retrotransposon-derived siRNAs in oocytes and germline small RNAs in testes. Genes Dev 20(13):1732–1743PubMedCrossRefGoogle Scholar
  102. Werner G, Werner K (1995) Immunocytochemical localization of histone H4 in the chromatoid body of rat spermatids. J Submicrosc Cytol Pathol 27(3):325–330PubMedGoogle Scholar
  103. Yang J, Medvedev S et al (2005a) The DNA/RNA-binding protein MSY2 marks specific transcripts for cytoplasmic storage in mouse male germ cells. Proc Natl Acad Sci USA 102(5):1513–1518PubMedCrossRefGoogle Scholar
  104. Yang J, Medvedev S et al (2005b) Absence of the DNA-/RNA-binding protein MSY2 results in male and female infertility. Proc Natl Acad Sci USA 102(16):5755–5760PubMedCrossRefGoogle Scholar
  105. Zhong J, Peters AH et al (1999) A double-stranded RNA binding protein required for activation of repressed messages in mammalian germ cells. Nat Genet 22(2):171–174PubMedCrossRefGoogle Scholar

Copyright information

© Springer Berlin Heidelberg 2011

Authors and Affiliations

  • Ippei Nagamori
    • 1
  • Adam Cruickshank
    • 1
  • Paolo Sassone-Corsi
    • 1
  1. 1.Department of Pharmacology, School of MedicineUniversity of CaliforniaIrvineUSA

Personalised recommendations