Conserved piRNA Expression from a Distinct Set of piRNA Cluster Loci in Eutherian Mammals

Abstract

The Piwi pathway is deeply conserved amongst animals because one of its essential functions is to repress transposons. However, many Piwi-interacting RNAs (piRNAs) do not base-pair to transposons and remain mysterious in their targeting function. The sheer number of piRNA cluster (piC) loci in animal genomes and infrequent piRNA sequence conservation also present challenges in determining which piC loci are most important for development. To address this question, we determined the piRNA expression patterns of piC loci across a wide phylogenetic spectrum of animals, and reveal that most genic and intergenic piC loci evolve rapidly in their capacity to generate piRNAs, regardless of known transposon silencing function. Surprisingly, we also uncovered a distinct set of piC loci with piRNA expression conserved deeply in Eutherian mammals. We name these loci Eutherian-Conserved piRNA cluster (ECpiC) loci. Supporting the hypothesis that conservation of piRNA expression across ~100 million years of Eutherian evolution implies function, we determined that one ECpiC locus generates abundant piRNAs antisense to the STOX1 transcript, a gene clinically associated with preeclampsia. Furthermore, we confirmed reduced piRNAs in existing mouse mutations at ECpiC-Asb1 and -Cbl, which also display spermatogenic defects. The Asb1 mutant testes with strongly reduced Asb1 piRNAs also exhibit up-regulated gene expression profiles. These data indicate ECpiC loci may be specially adapted to support Eutherian reproduction.

Domestic chickens activate a piRNA defense against avian leukosis virus

“…These piRNA clusters were distributed on most autosomes and the Z chromosome (Figure 1D). Unlike divergently and uni-directionally transcribed mouse piRNA-producing loci, we observed that chicken piRNAs were produced from both strands of piRNA clusters (Figure 4B, Figure 4—figure supplement 1A) as reported previously (Li et al, 2013; Chirn et al, 2015), and were derived from convergently transcribed precursors detected by our RNA-seq data (Figure 4B, Figure 4—figure supplement 1A). Over 70% of clusters (1173 out of 1633) included uniquely mapping piRNAs transcribed from either strand at a level of greater than 10% of total uniquely mapping piRNAs from that cluster.…”

“…Chicken piRNAs exhibit unique hybrid features of piRNAs found in other organisms. For example, the convergent transcription of piRNA-producing loci resembles the dual strands in fruit flies (Brennecke et al, 2007; Malone et al, 2009), but is distinct from that in frog (Chirn et al, 2015), zebrafish (Houwing et al, 2007), and mice (Li et al, 2013). However, unlike piRNAs in fruit flies and zebrafish that derive mainly from TEs, fewer than 10% of chicken piRNAs come from TE regions.…”

Two modes of targeting transposable elements by piRNA pathway in human testis

“…We also compared this method with the probabilistic algorithm proposed by Rosenkranz and Zischler (2012) and the meta-analysis performed by Chirn et al (2015). As a matter of fact, overlap among the three sets of clusters (empirical, probabilistic, and from the meta-analysis) was as high as 80%-100% (median: 94%, Supplemental Table S1C).…”

“…Probabilistic piRNA cluster calling was done with TBr2_duster.pl/sRNAmapper.pl/ proTRAC_2.1.2.pl pipeline by Rosenkranz and Zischler (Rosenkranz 2016;Rosenkranz and Zischler 2012) with proTRAC parameters as follows: -pdens 0.05 -1Tor10A 0.1 -1Tand10A 0.1 -clstrand 0.5 -clsplit 0.05. Finally, a list of 1299 of human piRNA clusters from meta-analysis by Chirn et al (2015) was also used. At the last filtering step, we kept only those empirical/probabilistic/meta-analysis clusters, whose piRNA coverage was higher than either 1RPKM or 10RPKM threshold, the fraction of 25-to 31-nt reads was at least 70%, and the length was more than 1 kb.…”

ARNs non-codants : potentiel d’utilisation thérapeutique

“…Les mutations des gènes impliqués dans cette machinerie induisent donc en général une dysfonction testiculaire totale, comme par exemple dans l'invalidation de Dnmt3l chez la souris (Bourc'his et al 2001). Les séquences répétées codant les piARNs évoluent très rapidement et sont peu conservées d'une espèce à l'autre pour la plupart (Chirn et al 2015).…”