Systemic RNA interference (RNAi) in Caenorhabditis elegans is initiated by SID-1-mediated double-stranded RNA (dsRNA) internalization. By combining cryo-electron microscopy (cryo-EM), in vitro and in vivo assays, we show how SID-1 specifically recognizes dsRNA and provide important insights into dsRNA internalization by SID-1.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Hannon, G. J. RNA interference. Nature 418, 244–251 (2002). A review article that presents the finding and mechanism of RNAi.
Winston, W. M., Molodowitch, C. & Hunter, C. P. Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science 295, 2456–2459 (2002). This paper reports that SID-1 is expressed in cells sensitive to RNAi and is required for systemic RNAi.
Feinberg, E. H. & Hunter, C. P. Transport of dsRNA into cells by the transmembrane protein SID-1. Science 301, 1545–1547 (2003). This paper reports that SID-1 mediates dsRNA transport in S2 cells and systemic RNAi in C. elegans.
Zheng, L. et al. Cryo-EM structures of human SID-1 transmembrane family proteins and implications for their low-pH-dependent RNA transport activity. Cell Res. 34, 80–83 (2024). This article describes human SIDT1 and SIDT2 structures and low-pH-dependent RNA binding to the isolated extracellular domain of SIDT1.
Qian, D. et al. Structural insight into the human SID1 transmembrane family member 2 reveals its lipid hydrolytic activity. Nat. Commun. 14, 3568 (2023). This article describes ceramidase activity of human SIDT2 with the conserved Zn2+ site as the catalytic center.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Zhang, J. et al. Structural insights into double-stranded RNA recognition and transport by SID-1. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-024-01276-9 (2024).
Rights and permissions
About this article
Cite this article
Cryo-EM structure reveals how SID-1 recognizes dsRNA that initiates systemic RNAi. Nat Struct Mol Biol (2024). https://doi.org/10.1038/s41594-024-01277-8
Published:
DOI: https://doi.org/10.1038/s41594-024-01277-8
