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Cited by 226Chromosomal and Genetic VariationsRNA Interference and Gene DeliveryPlant Molecular Biology Research

Identification of piRNA Binding Sites Reveals the Argonaute Regulatory Landscape of the C. elegans Germline

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Shen, En-Zhi, Chen, Hao, Ozturk, Ahmet R., Tu, Shikui, Shirayama, Masaki, Tang, Wen, Ding, Yue-He, Dai, Si-Yuan +2 more·2018·Cell
DOI 10.1016/j.cell.2018.02.002PMC PMC5905434

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Abstract

piRNAs (Piwi-interacting small RNAs) engage Piwi Argonautes to silence transposons and promote fertility in animal germlines. Genetic and computational studies have suggested that C. elegans piRNAs tolerate mismatched pairing and in principle could target every transcript. Here we employ in vivo cross-linking to identify transcriptome-wide interactions between piRNAs and target RNAs. We show that piRNAs engage all germline mRNAs and that piRNA binding follows microRNA-like pairing rules. Targeting correlates better with binding energy than with piRNA abundance, suggesting that piRNA concentration does not limit targeting. In mRNAs silenced by piRNAs, secondary small RNAs accumulate at the center and ends of piRNA binding sites. In germline-expressed mRNAs, however, targeting by the CSR-1 Argonaute correlates with reduced piRNA binding density and suppression of piRNA-associated secondary small RNAs. Our findings reveal physiologically important and nuanced regulation of individual piRNA targets and provide evidence for a comprehensive post-transcriptional regulatory step in germline gene expression.

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  • Other small regulatory RNAs, including piRNAs and snoRNAs, play critical roles in regulating RNA processing through interaction with complementary sequences.

    “there exist many other small regulatory RNAs that play critical roles in regulating RNA processing through interaction with complementary sequences, including piRNAs, snoRNAs, and others (Gumienny et al., 2017;Shen et al., 2018).”

    From Scalable and deep profiling of mRNA targets for individual microRNAs with chimeric eCLIP (2022) · cites this paper as Shen et al., 2018

    The Abstract and Discussion (pages not provided) show that piRNAs bind target RNAs through sequence pairing and participate in post-transcriptional regulation of germline gene expression. The paper does not establish that piRNAs regulate RNA processing specifically, and the passages do not address snoRNAs. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • CLASH with PIWI protein has been used to reveal mechanisms of piRNA targeting, and CLASH using E. Coli Hfq to enrich for sRNA-mRNA interactions revealed principles of small RNAs in bacteria.

    “CLASH with PIWI protein has been used to reveal mechanisms of piRNA targeting (Shen et al., 2018), and CLASH using E. Coli Hfq to enrich for sRNA-mRNA interactions revealed principles of small RNAs in bacteria (Iosub et al., 2020).”

    From Scalable and deep profiling of mRNA targets for individual microRNAs with chimeric eCLIP (2022) · cites this paper as Shen et al., 2018

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Cited by

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Authors
Shen, E.-Z., Chen, H., Ozturk, A. R., Tu, S., Shirayama, M., Tang, W., Ding, Y.-H., Dai, S.-Y., Weng, Z., & Mello, C. C.
Affiliations
  • University of Massachusetts Chan Medical School (US)
  • Boston University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Mello, Craig C.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2018-02
Volume
172
Issue
5
Pages
937-951.e18
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2018.02.002
PMC
PMC5905434
OpenAlex
W2788865254
Cited by
226
References
5
Citations by year
2026: 12 · 2025: 22 · 2024: 22 · 2023: 17 · 2022: 35 · 2021: 45 · 2020: 35 · 2019: 21 · 2018: 17
FWCI
26.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders
National Institutes of Health (GM124460, HD078253, GM058800)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
Keywords
piRNA, Argonaute proteins, CSR-1, germline, Caenorhabditis elegans, transposon silencing, post-transcriptional regulation, in vivo cross-linking, germline gene expression
MeSH terms
Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Chimera, Germ Cells, RNA, Messenger, Caenorhabditis elegans, Base Pairing, Gene Silencing, Caenorhabditis elegans Proteins, RNA, Small Interfering

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