RG motifs promote piRNA-mediated gene silencing in C. elegans
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Abstract
Argonaute proteins are essential components of RNA silencing pathways, and their N-terminal extensions, particularly in the PIWI clade, often harbor conserved RG motifs. Despite their prevalence, the function of these motifs remains poorly understood. In this study, we investigate the RG motifs in the N-terminal region of Caenorhabditis elegans PRG-1, a PIWI clade Argonaute. Sequence alignment across Caenorhabditis species reveals three conserved RG motifs, which we confirm to be methylated by mass spectrometry. The region surrounding these motifs is intrinsically disordered, as predicted by disorder algorithms and structural modeling. While the RG motifs are critical for fertility, germline morphology, and Piwi-interacting RNAs (piRNAs) silencing, they are not required for PRG-1 expression, localization, or piRNA loading. Notably, mutation of the RG motifs results in defects in downstream small RNA production, specifically the depletion of WAGO-class small interfering RNAs (siRNAs), without affecting piRNA biogenesis. These findings suggest that the RG motifs of PRG-1 play a crucial role in linking piRNA-mediated silencing to siRNA production, and that their function is critical for fertility and germline maintenance in C. elegans. Despite these defects, the phenotypic severity in the RG mutant is milder than in a PRG-1 null mutant, highlighting the complexity of PRG-1 function and its post-translational modifications.
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piRNA: Molecular Mechanisms from Germline Silencing to Somatic Regulation and Roles in Disease
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Germline fate determination by a single ARGONAUTE protein in Ectocarpus
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The splicing axis of aging: mechanisms and therapeutic opportunities
Raza, S., Kumari, A., & Cieśla, M. (2026) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2026.09.001
- Authors
- Wallis, D. C., & Phillips, C. M.
- Affiliations
- University of Southern California (US)
- Corresponding author
- Phillips, Carolyn M
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2025-11-26
- Volume
- 53
- Issue
- 22
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC12714567
- OpenAlex
- W4417524077
- Cited by
- 3
- References
- 115
- Citations by year
- 2026: 3
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (submittedVersion, cc-by-nd)
- PubMed Central (submittedVersion, cc-by-nd)
- Funders
- National Institutes of Health (R35 GM119656)
- Chemistry-Biology Interface
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- PRG-1, siRNA, intrinsically disordered regions, protein methylation, fertility, Caenorhabditis elegans, RNA silencing
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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