The splicing landscape is globally reprogrammed during male meiosis

Nucleic Acids Research

Volumn 41, Issue 22, 2013, Pages 10170-10184

  Schmid, Ralf ^a   Grellscheid, Sushma Nagaraja ^b,c   Ehrmann, Ingrid ^b   Dalgliesh, Caroline ^b   Danilenko, Marina ^b   Paronetto, Maria Paola ^d,e   Pedrotti, Simona ^e,f   Grellscheid, David ^c   Dixon, Richard J ^g   Sette, Claudio ^e,f   Eperon, Ian C ^a   Elliott, David J ^b  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

^c DURHAM UNIVERSITY   (United Kingdom)

^d UNIVERSITY OF ROME FORO ITALICO   (Italy)

^e IRCCS FONDAZIONE SANTA LUCIA   (Italy)

^f UNIVERSITY OF ROME TOR VERGATA   (Italy)

^g Life Technologies Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A1; MUSCLEBLIND; POLYPYRIMIDINE TRACT BINDING PROTEIN; PROTEIN CELF; PROTEIN SAM68; PROTEIN STAR; PROTEIN TRA2 BETA; REGULATOR PROTEIN; RNA; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BINDING SITE; CELL DIFFERENTIATION; CONTROLLED STUDY; DOWN REGULATION; EXON; GENE CASSETTE; GENE EXPRESSION; MALE; MEIOSIS; MOLECULAR MECHANICS; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; REGULATOR GENE; RNA SEQUENCE; RNA SPLICING; SPERMATOCYTE; SPERMATOGONIUM; TRANSCRIPTOMICS; UPREGULATION;

ALTERNATIVE SPLICING; ANIMALS; BASE SEQUENCE; EXONS; MALE; MEIOSIS; MICE; MOLECULAR SEQUENCE DATA; RNA ISOFORMS; RNA-BINDING PROTEINS; SEQUENCE ANALYSIS, RNA; SPERMATOCYTES; SPERMATOGONIA; TESTIS; TRANSCRIPTOME;

EID: 84890322979     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkt811     Document Type: Article

References (83)

1. Kwan, T., Benovoy, D., Dias, C., Gurd, S., Provencher, C., Beaulieu, P., Hudson, T.J., Sladek, R. and Majewski, J. (2008) Genome-wide analysis of transcript isoform variation in humans. Nat. Genet., 40, 225-231.
2. Mortazavi, A., Williams, B.A., McCue, K., Schaeffer, L. and Wold, B. (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat. Methods, 5, 621-628.
3. Pan, Q., Shai, O., Lee, L.J., Frey, B.J. and Blencowe, B.J. (2008) Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat. Genet., 40, 1413-1415.
4. Dreszer, T.R., Karolchik, D., Zweig, A.S., Hinrichs, A.S., Raney, B.J., Kuhn, R.M., Meyer, L.R., Wong, M., Sloan, C.A., Rosenbloom, K.R. et al. (2012) The UCSC Genome Browser database: extensions and updates 2011. Nucleic Acids Res., 40, D918-D923.
5. Djebali, S., Davis, C.A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., Tanzer, A., Lagarde, J., Lin, W., Schlesinger, F. et al. (2012) Landscape of transcription in human cells. Nature, 489, 101-108.
6. Llorian, M. and Smith, C.W. (2011) Decoding muscle alternative splicing. Curr. Opin. Genet. Dev., 21, 380-387.
7. Bland, C.S., Wang, E.T., Vu, A., David, M.P., Castle, J.C., Johnson, J.M., Burge, C.B. and Cooper, T.A. (2010) Global regulation of alternative splicing during myogenic differentiation. Nucleic Acids Res., 38, 7651-7664.
8. Ip, J.Y., Tong, A., Pan, Q., Topp, J.D., Blencowe, B.J. and Lynch, K.W. (2007) Global analysis of alternative splicing during T-cell activation. RNA, 13, 563-572.
9. Kalsotra, A., Xiao, X., Ward, A.J., Castle, J.C., Johnson, J.M., Burge, C.B. and Cooper, T.A. (2008) A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart. Proc. Natl Acad. Sci. USA, 105, 20333-20338.
10. McKee, A.E., Neretti, N., Carvalho, L.E., Meyer, C.A., Fox, E.A., Brodsky, A.S. and Silver, P.A. (2007) Exon expression profiling reveals stimulus-mediated exon use in neural cells. Genome Biol., 8, R159.
11. Fagnani, M., Barash, Y., Ip, J.Y., Misquitta, C., Pan, Q., Saltzman, A.L., Shai, O., Lee, L., Rozenhek, A., Mohammad, N. et al. (2007) Functional coordination of alternative splicing in the mammalian central nervous system. Genome Biol., 8, R108.
12. Kalsotra, A. and Cooper, T.A. (2011) Functional consequences of developmentally regulated alternative splicing. Nat. Rev. Genet., 12, 715-729.
13. Kan, Z., Garrett-Engele, P.W., Johnson, J.M. and Castle, J.C. (2005) Evolutionarily conserved and diverged alternative splicing events show different expression and functional profiles. Nucleic Acids Res., 33, 5659-5666.
14. Monesi, V. (1964) Ribonucleic acid synthesis during mitosis and meiosis in the mouse testis. J. Cell Biol., 22, 521-532.
15. Munding, E.M., Igel, A.H., Shiue, L., Dorighi, K.M., Trevino, L.R. and Ares, M. Jr (2010) Integration of a splicing regulatory network within the meiotic gene expression program of Saccharomyces cerevisiae. Genes Dev., 24, 2693-2704.
16. Fiume, M., Williams, V., Brook, A. and Brudno, M. (2010) Savant: genome browser for high-throughput sequencing data. Bioinformatics, 26, 1938-1944.
17. Russell, L.D., Ettlin, R., Sinha-Hikim, A.P. and Clegg, E.D. (1990) Histological and Histopathological Evaluation of the Testis. Cache River Press, Clearwater, FL.
18. Chalmel, F., Rolland, A.D., Niederhauser-Wiederkehr, C., Chung, S.S., Demougin, P., Gattiker, A., Moore, J., Patard, J.J., Wolgemuth, D.J., Jegou, B. et al. (2007) The conserved transcriptome in human and rodent male gametogenesis. Proc. Natl Acad. Sci. USA, 104, 8346-8351.
19. Clemente, E.J., Furlong, R.A., Loveland, K.L. and Affara, N.A. (2006) Gene expression study in the juvenile mouse testis: identification of stage-specific molecular pathways during spermatogenesis. Mamm. Genome, 17, 956-975.
20. Ellis, P.J., Furlong, R.A., Wilson, A., Morris, S., Carter, D., Oliver, G., Print, C., Burgoyne, P.S., Loveland, K.L. and Affara, N.A. (2004) Modulation of the mouse testis transcriptome during postnatal development and in selected models of male infertility. Mol. Hum. Reprod., 10, 271-281.
21. Lee, K., Haugen, H.S., Clegg, C.H. and Braun, R.E. (1995) Premature translation of protamine 1 mRNA causes precocious nuclear condensation and arrests spermatid differentiation in mice. Proc. Natl Acad. Sci. USA, 92, 12451-12455.
22. Melamud, E. and Moult, J. (2009) Stochastic noise in splicing machinery. Nucleic Acids Res., 37, 4873-4886.
23. Kamma, H., Portman, D.S. and Dreyfuss, G. (1995) Cell typespecific expression of hnRNP proteins. Exp. Cell Res., 221, 187-196.
24. Xu, M. and Hecht, N.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, 1025-1033.
25. Elliott, D.J., Oghene, K., Makarov, G., Makarova, O., Hargreave, T.B., Chandley, A.C., Eperon, I.C. and Cooke, H.J. (1998) Dynamic changes in the subnuclear organisation of premRNA splicing proteins and RBM during human germ cell development. J. Cell Sci., 111(Pt 9), 1255-1265.
26. Elliott, D.J., Venables, J.P., Newton, C.S., Lawson, D., Boyle, S., Eperon, I.C. and Cooke, H.J. (2000) An evolutionarily conserved germ cell-specific hnRNP is encoded by a retrotransposed gene. Hum. Mol. Genet., 9, 2117-2124.
27. Grellscheid, S., Dalgliesh, C., Storbeck, M., Best, A., Liu, Y., Jakubik, M., Mende, Y., Ehrmann, I., Curk, T., Rossbach, K. et al. (2011) Identification of evolutionarily conserved exons as regulated targets for the splicing activator tra2beta in development. PLoS Genet., 7, e1002390.
28. Paronetto, M.P., Zalfa, F., Botti, F., Geremia, R., Bagni, C. and Sette, C. (2006) The nuclear RNA-binding protein Sam68 translocates to the cytoplasm and associates with the polysomes in mouse spermatocytes. Mol. Biol. Cell, 17, 14-24.
29. Venables, J.P., Dalgliesh, C., Paronetto, M.P., Skitt, L., Thornton, J.K., Saunders, P.T., Sette, C., Jones, K.T. and Elliott, D.J. (2004) SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome. Hum. Mol. Genet., 13, 1525-1534.
30. Robida, M., Sridharan, V., Morgan, S., Rao, T. and Singh, R. (2010) Drosophila polypyrimidine tract-binding protein is necessary for spermatid individualization. Proc. Natl Acad. Sci. USA, 107, 12570-12575.
31. Robida, M.D. and Singh, R. (2003) Drosophila polypyrimidine-tract binding protein (PTB) functions specifically in the male germline. EMBO J., 22, 2924-2933.
32. Wang, L., Feng, Z., Wang, X. and Zhang, X. (2010) DEGseq: an R package for identifying differentially expressed genes from RNAseq data. Bioinformatics, 26, 136-138.
33. Anders, S. and Huber, W. (2010) Differential expression analysis for sequence count data. Genome Biol., 11, R106.
34. Young, M.D., Wakefield, M.J., Smyth, G.K. and Oshlack, A. (2010) Gene ontology analysis for RNA-seq: accounting for selection bias. Genome Biol., 11, R14.
35. Katz, Y., Wang, E.T., Airoldi, E.M. and Burge, C.B. (2010) Analysis and design of RNA sequencing experiments for identifying isoform regulation. Nat. Methods, 7, 1009-1015.
36. Wang, E.T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S.F., Schroth, G.P. and Burge, C.B. (2008) Alternative isoform regulation in human tissue transcriptomes. Nature, 456, 470-476.
37. Trapnell, C., Pachter, L. and Salzberg, S.L. (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics, 25, 1105-1111.
38. Cherny, D., Gooding, C., Eperon, G.E., Coelho, M.B., Bagshaw, C.R., Smith, C.W. and Eperon, I.C. (2010) Stoichiometry of a regulatory splicing complex revealed by single-molecule analyses. EMBO J., 29, 2161-2172.
39. Rossi, P., Dolci, S., Albanesi, C., Grimaldi, P., Ricca, R. and Geremia, R. (1993) Follicle-stimulating hormone induction of steel factor (SLF) mRNA in mouse Sertoli cells and stimulation of DNA synthesis in spermatogonia by soluble SLF. Dev. Biol., 155, 68-74.
40. Grimaldi, P., Piscitelli, D., Albanesi, C., Blasi, F., Geremia, R. and Rossi, P. (1993) Identification of 3', 5'-cyclic adenosine monophosphate- inducible nuclear factors binding to the human urokinase promoter in mouse Sertoli cells. Mol. Endocrinol., 7, 1217-1225.
41. Sette, C., Barchi, M., Bianchini, A., Conti, M., Rossi, P. and Geremia, R. (1999) Activation of the mitogen-activated protein kinase ERK1 during meiotic progression of mouse pachytene spermatocytes. J. Biol. Chem., 274, 33571-33579.
42. Elliott, D.J., Millar, M.R., Oghene, K., Ross, A., Kiesewetter, F., Pryor, J., McIntyre, M., Hargreave, T.B., Saunders, P.T., Vogt, P.H. et al. (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.
43. Fujita, P.A., Rhead, B., Zweig, A.S., Hinrichs, A.S., Karolchik, D., Cline, M.S., Goldman, M., Barber, G.P., Clawson, H., Coelho, A. et al. (2011) The UCSC Genome Browser database: update 2011. Nucleic Acids Res., 39, D876-D882.
44. Hertel, K.J. (2008) Combinatorial control of exon recognition. J. Biol. Chem., 283, 1211-1215.
45. Smith, C.W. and Valcarcel, J. (2000) Alternative pre-mRNA splicing: the logic of combinatorial control. Trends Biochem. Sci., 25, 381-388.
46. Gromak, N., Rideau, A., Southby, J., Scadden, A.D., Gooding, C., Huttelmaier, S., Singer, R.H. and Smith, C.W. (2003) The PTB interacting protein raver1 regulates alpha-tropomyosin alternative splicing. EMBO J., 22, 6356-6364.
47. Ehrmann, I., Dalgliesh, C., Tsaousi, A., Paronetto, M.P., Heinrich, B., Kist, R., Cairns, P., Li, W., Mueller, C., Jackson, M. et al. (2008) Haploinsufficiency of the germ cell-specific nuclear RNA binding protein hnRNP G-T prevents functional spermatogenesis in the mouse. Hum. Mol. Genet., 17, 2803-2818.
48. Gooding, C., Edge, C., Lorenz, M., Coelho, M.B., Winters, M., Kaminski, C.F., Cherny, D., Eperon, I.C. and Smith, C.W. (2013) MBNL1 and PTB cooperate to repress splicing of Tpm1 exon 3. Nucleic Acids Res., 41, 4765-4782.
49. Papoutsopoulou, S., Nikolakaki, E., Chalepakis, G., Kruft, V., Chevaillier, P. and Giannakouros, T. (1999) SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1. Nucleic Acids Res., 27, 2972-2980.
50. Kafasla, P., Mickleburgh, I., Llorian, M., Coelho, M., Gooding, C., Cherny, D., Joshi, A., Kotik-Kogan, O., Curry, S., Eperon, I.C. et al. (2012) Defining the roles and interactions of PTB. Biochem. Soc. Trans., 40, 815-820.
51. Oberstrass, F.C., Auweter, S.D., Erat, M., Hargous, Y., Henning, A., Wenter, P., Reymond, L., Amir-Ahmady, B., Pitsch, S., Black, D.L. et al. (2005) Structure of PTB bound to RNA: specific binding and implications for splicing regulation. Science, 309, 2054-2057.
52. Barash, Y., Calarco, J.A., Gao, W., Pan, Q., Wang, X., Shai, O., Blencowe, B.J. and Frey, B.J. (2010) Deciphering the splicing code. Nature, 465, 53-59.
53. Llorian, M., Schwartz, S., Clark, T.A., Hollander, D., Tan, L.Y., Spellman, R., Gordon, A., Schweitzer, A.C., de la Grange, P., Ast, G. et al. (2010) Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB. Nat. Struct. Mol. Biol., 17, 1114-1123.
54. Xue, Y., Zhou, Y., Wu, T., Zhu, T., Ji, X., Kwon, Y.S., Zhang, C., Yeo, G., Black, D.L., Sun, H. et al. (2009) Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping. Mol. Cell, 36, 996-1006.
55. Clery, A., Jayne, S., Benderska, N., Dominguez, C., Stamm, S. and Allain, F.H. (2011) Molecular basis of purine-rich RNA recognition by the human SR-like protein Tra2-beta1. Nat. Struct. Mol. Biol., 18, 443-450.
56. Tsuda, K., Someya, T., Kuwasako, K., Takahashi, M., He, F., Unzai, S., Inoue, M., Harada, T., Watanabe, S., Terada, T. et al. (2011) Structural basis for the dual RNA-recognition modes of human Tra2-beta RRM. Nucleic Acids Res., 39, 1538-1553.
57. Galarneau, A. and Richard, S. (2009) The STAR RNA binding proteins GLD-1, QKI, SAM68 and SLM-2 bind bipartite RNA motifs. BMC Mol. Biol., 10, 47.
58. Lin, Q., Taylor, S.J. and Shalloway, D. (1997) Specificity and determinants of Sam68 RNA binding. Implications for the biological function of K homology domains. J. Biol. Chem., 272, 27274-27280.
59. Stoss, O., Olbrich, M., Hartmann, A.M., Konig, H., Memmott, J., Andreadis, A. and Stamm, S. (2001) The STAR/GSG family protein rSLM-2 regulates the selection of alternative splice sites. J. Biol. Chem., 276, 8665-8673.
60. Venables, J.P., Vernet, C., Chew, S.L., Elliott, D.J., Cowmeadow, R.B., Wu, J., Cooke, H.J., Artzt, K. and Eperon, I.C. (1999) T-STAR/ETOILE: a novel relative of SAM68 that interacts with an RNA-binding protein implicated in spermatogenesis. Hum. Mol. Genet., 8, 959-969.
61. Keren, H., Lev-Maor, G. and Ast, G. (2010) Alternative splicing and evolution: diversification, exon definition and function. Nat. Rev. Genet., 11, 345-355.
62. Boutz, P.L., Stoilov, P., Li, Q., Lin, C.H., Chawla, G., Ostrow, K., Shiue, L., Ares, M. Jr and Black, D.L. (2007) A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev., 21, 1636-1652.
63. Lillevali, K., Kulla, A. and Ord, T. (2001) Comparative expression analysis of the genes encoding polypyrimidine tract binding protein (PTB) and its neural homologue (brPTB) in prenatal and postnatal mouse brain. Mech. Dev., 101, 217-220.
64. Licatalosi, D.D., Yano, M., Fak, J.J., Mele, A., Grabinski, S.E., Zhang, C. and Darnell, R.B. (2012) Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain. Genes Dev., 26, 1626-1642.
65. Markovtsov, V., Nikolic, J.M., Goldman, J.A., Turck, C.W., Chou, M.Y. and Black, D.L. (2000) Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein. Mol. Cell. Biol., 20, 7463-7479.
66. Polydorides, A.D., Okano, H.J., Yang, Y.Y., Stefani, G. and Darnell, R.B. (2000) A brain-enriched polypyrimidine tract-binding protein antagonizes the ability of Nova to regulate neuron-specific alternative splicing. Proc. Natl Acad. Sci. USA, 97, 6350-6355.
67. Tang, Z.Z., Sharma, S., Zheng, S., Chawla, G., Nikolic, J. and Black, D.L. (2011) Regulation of the mutually exclusive exons 8a and 8 in the CaV1.2 calcium channel transcript by polypyrimidine tract-binding protein. J. Biol. Chem., 286, 10007-10016.
68. Spellman, R., Llorian, M. and Smith, C.W. (2007) Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1. Mol. Cell, 27, 420-434.
69. Stoilov, P., Daoud, R., Nayler, O. and Stamm, S. (2004) Human tra2-beta1 autoregulates its protein concentration by influencing alternative splicing of its pre-mRNA. Hum. Mol. Genet., 13, 509-524.
70. Paronetto, M.P., Messina, V., Barchi, M., Geremia, R., Richard, S. and Sette, C. (2011) Sam68 marks the transcriptionally active stages of spermatogenesis and modulates alternative splicing in male germ cells. Nucleic Acids Res., 39, 4961-4974.
71. Paronetto, M.P., Messina, V., Bianchi, E., Barchi, M., Vogel, G., Moretti, C., Palombi, F., Stefanini, M., Geremia, R., Richard, S. et al. (2009) Sam68 regulates translation of target mRNAs in male germ cells, necessary for mouse spermatogenesis. J. Cell Biol., 185, 235-249.
72. Richard, S., Torabi, N., Franco, G.V., Tremblay, G.A., Chen, T., Vogel, G., Morel, M., Cleroux, P., Forget-Richard, A., Komarova, S. et al. (2005) Ablation of the Sam68 RNA binding protein protects mice from age-related bone loss. PLoS Genet., 1, e74.
73. Kress, C., Gautier-Courteille, C., Osborne, H.B., Babinet, C. and Paillard, L. (2007) Inactivation of CUG-BP1/CELF1 causes growth, viability, and spermatogenesis defects in mice. Mol. Cell. Biol., 27, 1146-1157.
74. Wang, G.S. and Cooper, T.A. (2007) Splicing in disease: disruption of the splicing code and the decoding machinery. Nat. Rev. Genet., 8, 749-761.
75. Huber, D., Geisler, S., Monecke, S. and Hoyer-Fender, S. (2008) Molecular dissection of ODF2/Cenexin revealed a short stretch of amino acids necessary for targeting to the centrosome and the primary cilium. Eur. J. Cell Biol., 87, 137-146.
76. Rivkin, E., Tres, L.L. and Kierszenbaum, A.L. (2008) Genomic origin, processing and developmental expression of testicular outer dense fiber 2 (ODF2) transcripts and a novel nucleolar localization of ODF2 protein. Mol. Reprod. Dev., 75, 1591-1606.
77. Alekseev, O.M., Richardson, R.T. and O'Rand, M.G. (2009) Linker histones stimulate HSPA2 ATPase activity through NASP binding and inhibit CDC2/Cyclin B1 complex formation during meiosis in the mouse. Biol. Reprod., 81, 739-748.
78. Richardson, R.T., Alekseev, O.M., Grossman, G., Widgren, E.E., Thresher, R., Wagner, E.J., Sullivan, K.D., Marzluff, W.F. and O'Rand, M.G. (2006) Nuclear autoantigenic sperm protein (NASP), a linker histone chaperone that is required for cell proliferation. J. Biol. Chem., 281, 21526-21534.
79. Richardson, R.T., Batova, I.N., Widgren, E.E., Zheng, L.X., Whitfield, M., Marzluff, W.F. and O'Rand, M.G. (2000) Characterization of the histone H1-binding protein, NASP, as a cell cycle-regulated somatic protein. J. Biol. Chem., 275, 30378-30386.
80. Di Meglio, T., Kratochwil, C.F., Vilain, N., Loche, A., Vitobello, A., Yonehara, K., Hrycaj, S.M., Roska, B., Peters, A.H., Eichmann, A. et al. (2013) Ezh2 orchestrates topographic migration and connectivity of mouse precerebellar neurons. Science, 339, 204-207.
81. Hinz, S., Magheli, A., Weikert, S., Schulze, W., Krause, H., Schrader, M., Miller, K. and Kempkensteffen, C. (2010) Deregulation of EZH2 expression in human spermatogenic disorders and testicular germ cell tumors. World J. Urol., 28, 631-635.
82. Lambrot, R., Jones, S., Saint-Phar, S. and Kimmins, S. (2012) Specialized distribution of the histone methyltransferase Ezh2 in the nuclear apical region of round spermatids and its interaction with the histone variant H1t2. J. Androl., 33, 1058-1066.
83. Leu, N.A., Kurosaka, S. and Kashina, A. (2009) Conditional Tek promoter-driven deletion of arginyltransferase in the germ line causes defects in gametogenesis and early embryonic lethality in mice. PLoS One, 4, e7734.