MORC3, a novel MIWI2 association partner, as an epigenetic regulator of piRNA dependent transposon silencing in male germ cells

Kanako Kojima-Kita,Satomi Kuramochi-Miyagawa,Haruhiko Koseki,Steven E Jacobsen,Masahito Ikawa,Toru Nakano,Haruhiko Miyata,Manabu Nakayama

doi:10.1038/s41598-021-98940-7

Abstract

The PIWI (P-element-induced wimpy testis)-interacting-RNA (piRNA) pathway plays a crucial role in the repression of TE (transposable element) expression via de novo DNA methylation in mouse embryonic male germ cells. Various proteins, including MIWI2 are involved in the process. TE silencing is ensured by piRNA-guided MIWI2 that recruits some effector proteins of the DNA methylation machinery to TE regions. However, the molecular mechanism underlying the methylation is complex and has not been fully elucidated. Here, we identified MORC3 as a novel associating partner of MIWI2 and also a nuclear effector of retrotransposon silencing via piRNA-dependent de novo DNA methylation in embryonic testis. Moreover, we show that MORC3 is important for transcription of piRNA precursors and subsequently affects piRNA production. Thus, we provide the first mechanistic insights into the role of this effector protein in the first stage of piRNA biogenesis in embryonic TE silencing mechanism.

Highlights

IntroductionThe PIWI (P-element-induced wimpy testis)-interacting-RNA (piRNA) pathway plays a crucial role in the repression of TE (transposable element) expression via de novo DNA methylation in mouse embryonic male germ cells
The PIWI (P-element-induced wimpy testis)-interacting-RNA pathway plays a crucial role in the repression of TE expression via de novo DNA methylation in mouse embryonic male germ cells
In Arabidopsis, AtMORC1 and AtMORC6 play a critical role in TE repression with heterochromatin formation at retrotransposon regions, and the process is independent of DNA methylation and repressive histone m odification[35,36]

Summary

Introduction

The PIWI (P-element-induced wimpy testis)-interacting-RNA (piRNA) pathway plays a crucial role in the repression of TE (transposable element) expression via de novo DNA methylation in mouse embryonic male germ cells. Embryonic piRNAs are germ cell-specific small noncoding RNAs of 25–31 nucleotides that bind to PIWI proteins and contribute to the silencing of TEs in the germlines. They are mostly derived from r etrotransposons[8,9,10,11]. MILI (PIWIL2) and MIWI2 (PIWIL4) are essential for spermatogenesis and play critical functions in piRNA biogenesis and de novo DNA methylation at the retrotransposon region, respectively[12,13,14,15]. MORC3 conventional knockout mice die at birth or within a day thereafter for unknown reasons and MORC3 is concluded to be essential for postnatal development[2]

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Conclusion