piRTarBase: a database of piRNA targeting sites and their roles in gene regulation

Abstract

PIWI-interacting RNAs (piRNAs) are a class of small noncoding RNAs that guard animal genomes against mutation by silencing transposons. In addition, recent studies have reported that piRNAs silence various endogenous genes. Tens of thousands of distinct piRNAs made in animals do not pair well to transposons and currently the functions and targets of piRNAs are largely unexplored. piRTarBase provides a user-friendly interface to access both predicted and experimentally identified piRNA targeting sites in Caenorhabditis elegans. The user can input genes of interest and retrieve a list of piRNA targeting sites on the input genes. Alternatively, the user can input a piRNA and retrieve a list of its mRNA targets. Additionally, piRTarBase integrates published mRNA and small RNA sequencing data, which will help users identify biologically relevant targeting events. Importantly, our analyses suggest that the piRNA sites found by both predictive and experimental approaches are more likely to exhibit silencing effects on their targets than each method alone. Taken together, piRTarBase offers an integrative platform that will help users to identify functional piRNA target sites by evaluating various information. piRTarBase is freely available for academic use at http://cosbi6.ee.ncku.edu.tw/piRTarBase/.

Caenorhabditis elegans ADAR editing and the ERI-6/7/MOV10 RNAi pathway silence endogenous viral elements and LTR retrotransposons

“…However, the predicted piRNAs lack features typical of piRNAs: they do not have a 5’U, they are not dependent on the PIWI protein PRG-1, they are completely dependent on mutator proteins (suggesting that these small RNAs are siRNAs) (e.g. mut-15 in Figure 3D), and in prg-1 mutants, the target of these piRNAs, Cer19 RNA is two- to five-fold downregulated (piRTarBase (24)).…”

Caenorhabditis elegans ADAR editing and the ERI-6/7/MOV10 RNAi pathway silence endogenous viral elements and LTR retrotransposons

“…However, these piRNAs lack features typical of piRNAs: they do not have a 5′U, they are not dependent on the PIWI protein PRG-1, they are completely dependent on mutator proteins (suggesting that these small RNAs are siRNAs, e.g., mut-15 in Fig. 3D), and, in prg-1 mutants, the target of these piRNAs, Cer19 RNA, is two-to fivefold down-regulated [piRTarBase (28)].…”

A Small-RNA-Mediated Feedback Loop Maintains Proper Levels of 22G-RNAs in C. elegans

“…Similar results were observed previously in hrde-1 single mutants ( Ni et al, 2014 ). Using piRTarBase, a database that curates both predicted and experimentally identified piRNA target sites, we found that the mRNA sequence of sosi-1 harbors 12 sequence-predicted piRNA-binding sites ( Wu et al, 2019 ; Zhang et al, 2018 ), suggesting that the MUT-16-dependent and HRDE-1-loaded 22G-RNAs mapping to the sosi-1 region may be initiated by piRNAs.…”

“…Because hrde-1 mutants were previously shown to exhibit reduced small RNA levels mapping to the eri-6[e – f] region ( Ni et al, 2014 ), we were unable to definitively conclude whether the HRDE-1-loaded 22G-RNAs are piRNA initiated. However, using piRTarBase, we found both sequence-predicted and cross-linking, ligation, and sequencing of hybrids (CLASH)-identified piRNA-binding sites within the mRNA sequences of eri-6 [e – f] (25 sequence predicted, 14 CLASH identified) and its paralog K09B11.4 (6 sequence predicted, 6 CLASH identified) ( Shen et al, 2018 ; Wu et al, 2019 ; Zhang et al, 2018 ), suggesting the HRDE-1-loaded 22G-RNAs may be piRNA initiated. The piRNAs identified as binding to K09B11.4 were also found to bind eri-6f transcripts ( Shen et al, 2018 ).…”