title: The mouse cytosine-5 RNA methyltransferase NSun2 is a component of the chromatoid body and required for testis differentiation.
abstract: Posttranscriptional regulatory mechanisms are crucial for protein synthesis during spermatogenesis and are often organized by the chromatoid body. Here, we identify the RNA methyltransferase NSun2 as a novel component of the chromatoid body and, further, show that NSun2 is essential for germ cell differentiation in the mouse testis. In NSun2-depleted testes, genes encoding Ddx4, Miwi, and Tudor domain-containing (Tdr) proteins are repressed, indicating that RNA-processing and posttranscriptional pathways are impaired. Loss of NSun2 specifically blocked meiotic progression of germ cells into the pachytene stage, as spermatogonial and Sertoli cells were unaffected in knockout mice. We observed the same phenotype when we simultaneously deleted NSun2 and Dnmt2, the only other cytosine-5 RNA methyltransferase characterized to date, indicating that Dnmt2 was not functionally redundant with NSun2 in spermatogonial stem cells or Sertoli cells. Specific NSun2- and Dnmt2-methylated tRNAs decreased in abundance when both methyltransferases were deleted, suggesting that RNA methylation pathways play an essential role in male germ cell differentiation.
authors: Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
authors: Shobbir
authors: S
authors: Hussain
authors: Francesca
authors: F
authors: Tuorto
authors: Suraj
authors: S
authors: Menon
authors: Sandra
authors: S
authors: Blanco
authors: Claire
authors: C
authors: Cox
authors: Joana V
authors: JV
authors: Flores
authors: Stephen
authors: S
authors: Watt
authors: Nobuaki R
authors: NR
authors: Kudo
authors: Frank
authors: F
authors: Lyko
authors: Michaela
authors: M
authors: Frye
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics; D002454:Cell Differentiation; D053487:DEAD-box RNA Helicases / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D049469:Meiotic Prophase I; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D049471:Pachytene Stage / Q000235:genetics; D011499:Protein Processing, Post-Translational; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics; D012708:Sertoli Cells / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics; D013093:Spermatogonia / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000166:cytology* / Q000201:enzymology
chemical_list: D060565:Argonaute Proteins; C448522:Piwil1 protein, mouse; D017411:Ribonucleoproteins, Small Nuclear; D012313:RNA; D012343:RNA, Transfer; C491786:Dnmt2 protein, mouse; D008780:Methyltransferases; C513146:Misu protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases; C090864:Ddx4 protein, mouse; D053487:DEAD-box RNA Helicases
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