Mouse GTSF1 is an essential factor for secondary piRNA biogenesis

Abstract

<p id="d5209780e496">The pi <span style="fixed-case">RNA</span> pathway is a pi <span style="fixed-case">RNA</span>‐guided retrotransposon silencing system which includes processing of retrotransposon transcripts by <span style="fixed-case">PIWI</span>‐pi <span style="fixed-case">RNA</span>s in secondary pi <span style="fixed-case">RNA</span> biogenesis. Although several proteins participate in the pi <span style="fixed-case">RNA</span> pathway, the ones crucial for the cleavage of target <span style="fixed-case">RNA</span>s by <span style="fixed-case">PIWI</span>‐pi <span style="fixed-case">RNA</span>s have not been identified. Here, we show that <span style="fixed-case">GTSF</span>1, an essential factor for retrotransposon silencing in male germ cells in mice, associates with both <span style="fixed-case">MILI</span> and <span style="fixed-case">MIWI</span>2, mouse <span style="fixed-case">PIWI</span> proteins that function in prospermatogonia. <span style="fixed-case">GTSF</span>1 deficiency leads to a severe defect in the production of secondary pi <span style="fixed-case">RNA</span>s, which are generated from target <span style="fixed-case">RNA</span>s of <span style="fixed-case">PIWI</span>‐pi <span style="fixed-case">RNA</span>s. Furthermore, in <i>Gtsf1</i> mutants, a known target <span style="fixed-case">RNA</span> of <span style="fixed-case">PIWI</span>‐pi <span style="fixed-case">RNA</span>s is left unsliced at the cleavage site, and the generation of secondary pi <span style="fixed-case">RNA</span>s from this transcript is defective. Our findings indicate that <span style="fixed-case">GTSF</span>1 is a crucial factor for the slicing of target <span style="fixed-case">RNA</span>s by <span style="fixed-case">PIWI</span>‐pi <span style="fixed-case">RNA</span>s and thus affects secondary pi <span style="fixed-case">RNA</span> biogenesis in prospermatogonia. </p>