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Title | Structural insights into double-stranded RNA recognition and transport by SID-1. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 31, Issue 7, Page 1095-1104, Year 2024 |
Publish date | Apr 25, 2024 |
Authors | Jiangtao Zhang / Chunhua Zhan / Junping Fan / Dian Wu / Ruixue Zhang / Di Wu / Xinyao Chen / Ying Lu / Ming Li / Min Lin / Jianke Gong / Daohua Jiang / |
PubMed Abstract | RNA uptake by cells is critical for RNA-mediated gene interference (RNAi) and RNA-based therapeutics. In Caenorhabditis elegans, RNAi is systemic as a result of SID-1-mediated double-stranded RNA ...RNA uptake by cells is critical for RNA-mediated gene interference (RNAi) and RNA-based therapeutics. In Caenorhabditis elegans, RNAi is systemic as a result of SID-1-mediated double-stranded RNA (dsRNA) across cells. Despite the functional importance, the underlying mechanisms of dsRNA internalization by SID-1 remain elusive. Here we describe cryogenic electron microscopy structures of SID-1, SID-1-dsRNA complex and human SID-1 homologs SIDT1 and SIDT2, elucidating the structural basis of dsRNA recognition and import by SID-1. The homodimeric SID-1 homologs share conserved architecture, but only SID-1 possesses the molecular determinants within its extracellular domains for distinguishing dsRNA from single-stranded RNA and DNA. We show that the removal of the long intracellular loop between transmembrane helix 1 and 2 attenuates dsRNA uptake and systemic RNAi in vivo, suggesting a possible endocytic mechanism of SID-1-mediated dsRNA internalization. Our study provides mechanistic insights into dsRNA internalization by SID-1, which may facilitate the development of dsRNA applications based on SID-1. |
External links | Nat Struct Mol Biol / PubMed:38664565 |
Methods | EM (single particle) |
Resolution | 2.77 - 3.71 Å |
Structure data | EMDB-34825, PDB-8hip: EMDB-34850, PDB-8hke: EMDB-36008, PDB-8j6m: EMDB-36009, PDB-8j6o: |
Chemicals | ChemComp-6OU: ChemComp-ZN: ChemComp-CLR: ChemComp-NA: ChemComp-OLA: ChemComp-HOH: ChemComp-NAG: |
Source |
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Keywords | RNA BINDING PROTEIN / dsRNA transporter / TRANSCRIPTION / transport T1 / TRANSPORT PROTEIN / transport T2 |