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Mitochondrial membrane-based initial separation of MIWI and MILI functions during pachytene piRNA biogenesis

Deqiang Ding1, Jiali Liu1,2, Kunzhe Dong3

  • 1Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA.

Nucleic Acids Research
|December 28, 2018
PubMed

Insights

Mitochondria-anchored TDRKH protein is crucial for piRNA biogenesis in mice. It recruits PIWI protein MIWI, ensuring germ cell development and preventing retrotransposon LINE1 de-repression.

Area of Science:

  • Molecular Biology
  • Genetics
  • Reproductive Biology

Background:

  • PIWI-interacting RNAs (piRNAs) are essential for silencing transposons and germ cell development.
  • piRNA biogenesis is linked to the mitochondrial surface, involving membrane-anchored factors.
  • The recruitment mechanism of PIWI proteins MIWI and MILI to the intermitochondrial cement (IMC) for piRNA processing remains unclear.

Purpose of the Study:

  • To elucidate the role of mitochondria-anchored factors in pachytene piRNA biogenesis.
  • To investigate how MIWI and MILI are recruited to the IMC and engage in piRNA processing.
  • To understand the function of TDRKH in the piRNA pathway and germ cell development.

Main Methods:

  • Mice models with TDRKH deficiency.
  • Immunofluorescence microscopy to visualize PIWI protein localization.
  • RNA sequencing to analyze piRNA populations.
  • Analysis of spermiogenesis and retrotransposon expression.

Main Results:

  • Mitochondria-anchored TDRKH specifically recruits MIWI, not MILI, to the IMC.
  • TDRKH is essential for the production of MIWI-bound piRNAs and trimming of MILI-bound piRNAs.
  • TDRKH deficiency leads to MIWI loss, spermiogenic arrest, and LINE1 de-repression.

Conclusions:

  • TDRKH acts as a mitochondrial surface scaffold, regulating PIWI protein recruitment and function in piRNA biogenesis.
  • This mechanism separates the roles of MIWI and MILI in the piRNA pathway, crucial for germ cell development.
  • TDRKH is vital for maintaining transposon silencing and ensuring successful spermiogenesis.

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