Mouse maelstrom, a component of nuage, is essential for spermatogenesis and transposon repression in meiosis

Dev Cell. 2008 Aug;15(2):285-97. doi: 10.1016/j.devcel.2008.05.015.

Abstract

Tight control of transposon activity is essential for the integrity of the germline. Recently, a germ-cell-specific organelle, nuage, was proposed to play a role in transposon repression. To test this hypothesis, we disrupted a murine homolog of a Drosophila nuage protein Maelstrom. Effects on male meiotic chromosome synapsis and derepression of transposable elements (TEs) were observed. In the adult Mael(-/-) testes, LINE-1 (L1) derepression occurred at the onset of meiosis. As a result, Mael(-/-) spermatocytes were flooded with L1 ribonucleoproteins (RNPs) that accumulated in large cytoplasmic enclaves and nuclei. Mael(-/-) spermatocytes with nuclear L1 RNPs exhibited massive DNA damage and severe chromosome asynapsis even in the absence of SPO11-generated meiotic double-strand breaks. This study demonstrates that MAEL, a nuage component, is indispensable for the silencing of TEs and identifies the initiation of meiosis as an important step in TE control in the male germline.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Cell Nucleus Structures / metabolism*
  • Cell Nucleus Structures / ultrastructure
  • Chromosome Pairing
  • Chromosomes, Mammalian / metabolism
  • DNA Breaks, Double-Stranded
  • DNA Methylation
  • DNA Transposable Elements*
  • DNA-Binding Proteins / metabolism*
  • Endodeoxyribonucleases
  • Esterases / metabolism
  • Gene Targeting
  • Male
  • Meiosis*
  • Mice
  • Mice, Inbred C57BL
  • Open Reading Frames / genetics
  • Protein Transport
  • Ribonucleoproteins / metabolism
  • Sex Chromosomes / metabolism
  • Spermatocytes / cytology
  • Spermatocytes / ultrastructure
  • Spermatogenesis*
  • Spermatozoa / cytology
  • Spermatozoa / ultrastructure
  • Testis / cytology
  • Testis / ultrastructure
  • Transcription Factors / metabolism*

Substances

  • DNA Transposable Elements
  • DNA-Binding Proteins
  • Ribonucleoproteins
  • Transcription Factors
  • maelstrom protein, mouse
  • Endodeoxyribonucleases
  • Esterases
  • meiotic recombination protein SPO11