FULL TITLE : Two modes of targeting transposable elements by 1 piRNA pathway in human testis 2 RUNNING TITLE : Targeting transposable elements by piRNA 3 pathway 4

12 PIWI proteins and their partner small RNAs, termed piRNAs, are known to control transposable 13 elements (TEs) in the germline. Here, we provide evidence that in humans this control is exerted in 14 two different modes. On the one hand, production of piRNAs specifically targeting evolutionarily 15 youngest TEs (L1HS, L1PA2-L1PA6, LTR12C, SVA) is present both at prenatal and postnatal stages 16 of spermatogenesis and is performed without involvement of piRNA clusters. On the other hand, at 17 postnatal stages, piRNAs deriving from pachytene clusters target “older” TEs and thus complement 18 cluster-independent piRNA production to achieve relevant targeting of virtually all TEs expressed in 19 postnatal testis. We also find that converging transcription of antisense-oriented genes contributes to 20 the origin of genic postnatal pre-pachytene clusters. Finally, while a fraction of pachytene piRNAs was 21 previously shown to arise from long intergenic non-coding RNAs (lincRNAs, i.e. pachytene piRNA 22 cluster primary transcripts), we ascertain that these are a specific set of lincRNAs that both possess 23 distinguishing epigenetic features and are expressed exclusively in testis. 24 INTRODUCTION 25 Cold Spring Harbor Laboratory Press on August 27, 2017 Published by rnajournal.cshlp.org Downloaded from