A highly selective mechanism to suppress retrotransposon expression in Drosophila

Hayashi R1, Handler D2, Brandstaetter S2, Helmrath S2, Felder AK2 and Brennecke J2

  1. The John Curtin School of Medical Research (JCSMR), The Australian National University, 131 Garran Road, Acton ACT 2601, Australia.
  2. Institute of Molecular Biotechnology of Austrian Academy of Sciences (IMBA), Dr Bohr-Gasse 3, 1030 Vienna, Austria.

A selective and plastic mechanism to silence parasitic genetic elements is pivotal to maintain the integrity of eukaryotic genomes. In the somatic compartment of fruit fly ovaries, gypsy class LTR-retrotransposons are suppressed by a class of small RNA called Piwi-interacting RNAs (piRNAs). piRNAs in this tissue are predominantly derived from a single precursor RNA called flamenco (flam), which is transcribed from the ~300 kb genomic locus that is enriched of gypsy-family transposon sequences. Although piRNAs are also derived from other cytoplasmic transcripts, flam RNA produces piRNAs far more efficiently (10 ~ 10^3 fold). The mechanism that underlies the selectivity is not known. In the present work, we show that the piRNA biogenesis factor Fs(1)Yb selects flam RNA against other RNAs. Upon depletion of Fs(1)Yb, flam-derived piRNAs are largely lost while other cellular RNAs including mRNAs become preferentially processed into piRNAs. Based on a computational analysis, we were able to uncover the underlying features in piRNA-precursor transcripts to recruit Fs(1)Yb. Our work therefore sheds light on the fundamental question of how the cell distinguishes self from non-self transcripts.