Journal article

HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse

Shu Ly Lim, Zhi Peng Qu, R Daniel Kortschak, David M Lawrence, Joel Geoghegan, Anna-Lena Hempfling, Martin Bergmann, Christopher C Goodnow, Christopher J Ormandy, Lee Wong, Jeff Mann, Hamish S Scott, Duangporn Jamsai, David L Adelson, Moira K O'Bryan

PLOS GENETICS | PUBLIC LIBRARY SCIENCE | Published : 2015

Abstract

piRNAs are critical for transposable element (TE) repression and germ cell survival during the early phases of spermatogenesis, however, their role in adult germ cells and the relative importance of piRNA methylation is poorly defined in mammals. Using a mouse model of HEN methyltransferase 1 (HENMT1) loss-of-function, RNA-Seq and a range of RNA assays we show that HENMT1 is required for the 2' O-methylation of mammalian piRNAs. HENMT1 loss leads to piRNA instability, reduced piRNA bulk and length, and ultimately male sterility characterized by a germ cell arrest at the elongating germ cell phase of spermatogenesis. HENMT1 loss-of-function, and the concomitant loss of piRNAs, resulted in TE ..

View full abstract

University of Melbourne Researchers

Grants

Funding Acknowledgements

This work was supported by grants from the Australian Research Council to MKO, HSS, DA and CJO; the New South Wales Cancer Council, Cancer Institute New South Wales, Banque Nationale de Paris-Paribas Australia and New Zealand, RT Hall Trust, and the National Breast Cancer Foundation to CJO, and the Deutsche Forschungsgemeinschaft as part of an International Research Training Group project. MKO, HSS, and CJO are NHMRC Fellows (1058356, 481310, 1023059). CCG is an NHMRC Australia Fellowship. SLL was the recipient of a Lalor Foundation Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.