piRNAs of Caenorhabditis elegans broadly silence nonself sequences through functionally random targeting.

TitlepiRNAs of Caenorhabditis elegans broadly silence nonself sequences through functionally random targeting.
Publication TypeJournal Article
Year of Publication2022
AuthorsMcEnany, J, Meir, Y, Wingreen, NS
JournalNucleic Acids Res
Date Published2022 Feb 22
KeywordsAnimals, Argonaute Proteins, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Drosophila melanogaster, RNA, Small Interfering

<p>Small noncoding RNAs such as piRNAs are guides for Argonaute proteins, enabling sequence-specific, post-transcriptional regulation of gene expression. The piRNAs of Caenorhabditis elegans have been observed to bind targets with high mismatch tolerance and appear to lack specific transposon targets, unlike piRNAs in Drosophila melanogaster and other organisms. These observations support a model in which C. elegans piRNAs provide a broad, indiscriminate net of silencing, competing with siRNAs associated with the CSR-1 Argonaute that specifically protect self-genes from silencing. However, the breadth of piRNA targeting has not been subject to in-depth quantitative analysis, nor has it been explained how piRNAs are distributed across sequence space to achieve complete coverage. Through a bioinformatic analysis of piRNA sequences, incorporating an original data-based metric of piRNA-target distance, we demonstrate that C. elegans piRNAs are functionally random, in that their coverage of sequence space is comparable to that of random sequences. By possessing a sufficient number of distinct, essentially random piRNAs, C. elegans is able to target arbitrary nonself sequences with high probability. We extend this approach to a selection of other nematodes, finding results which elucidate the mechanism by which nonself mRNAs are silenced, and have implications for piRNA evolution and biogenesis.</p>

Alternate JournalNucleic Acids Res
PubMed ID35037068
PubMed Central IDPMC8860604
Grant ListT32 GM136568 / GM / NIGMS NIH HHS / United States