Abstract

PIWI-interacting RNAs (piRNAs) are regarded as the guardians of the genome because they tackle genome stability-threatening transposable elements in the germline. Recently, piRNAs were also reported in other types of cells, including mouse brain, malignant and non-malignant somatic tissues, and human plasma. This suggests that piRNA function might be broader than previously expected. Here, we show that different piRNA databases contain a subset of sequences that correspond to piRNA-sized fragments of ncRNAs (rRNAs, tRNAs, YRNAs, snRNAs, and snoRNAs) and intermediates of miRNA biogenesis. We discuss that the biogenesis of these sequences is probably independent of the PIWI pathway, and can therefore be considered contaminants in piRNA databases. Although a minority of annotated piRNAs falls in this category, they account for the vast majority of piRNA expression in somatic non-gonadal tissues. Since ncRNA fragments are ubiquitous and abundant, their confusion with piRNAs strongly impacts the estimation of piRNA expression outside of mammalian gonads.

Highlights

  • PIWI-interacting RNAs are regarded as the guardians of the genome because they tackle genome stability-threatening transposable elements in the germline

  • Analysis of these sequences showed a strong bias for uridine at the first position (1 T in our data set), in accordance with the preferential binding of PIWI proteins to transcripts starting with U (Fig. 1a)

  • To study the overlap between the PIWI-interacting RNAs (piRNAs) sequences contained in these databases and other non-coding RNAs, we aligned each sequence against genomic or mitochondria-encoded tRNAs, rRNAs, snRNAs, snoRNAs, YRNAs, and miRNAs

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Summary

Introduction

PIWI-interacting RNAs (piRNAs) are regarded as the guardians of the genome because they tackle genome stability-threatening transposable elements in the germline. PiRNAs were reported in other types of cells, including mouse brain, malignant and nonmalignant somatic tissues, and human plasma This suggests that piRNA function might be broader than previously expected. Argonaute proteins are phylogenetically subdivided into two subclasses, comprising the orthologs of Arabidopsis AGO1 and Drosophila Piwi (defining AGO and PIWI subfamilies, respectively)[2] While the former are involved in posttranscriptional gene silencing by siRNAs and miRNAs, the biological function of PIWI proteins was initially unclear, they were shown early on to be essential for germ cell maintenance[3, 4]. Drosophila PIWI proteins were shown to bind repeat-associated siRNAs, a germline-enriched 24–29 nt small RNA family previously known to be involved in transposon silencing[8], in the Drosophila ovary This led to the notion that the conserved function of piRNAs is to tackle genome stabilitythreatening transposable elements in the germline[9,10,11]. The sequences of these tRNA halves are nearly identical, with only one nucleotide variation in sequence length, to annotated piRNAs (NCBI accession: DQ597916.1 and DQ570956.1)

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