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Structure paper

TitleStructural insights into double-stranded RNA recognition and transport by SID-1.
Journal, issue, pagesNat Struct Mol Biol, Year 2024
Publish dateApr 25, 2024
AuthorsJiangtao Zhang / Chunhua Zhan / Junping Fan / Dian Wu / Ruixue Zhang / Di Wu / Xinyao Chen / Ying Lu / Ming Li / Min Lin / Jianke Gong / Daohua Jiang /
PubMed AbstractRNA 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 linksNat Struct Mol Biol / PubMed:38664565
MethodsEM (single particle)
Resolution2.77 - 3.71 Å
Structure data

34825

8hip

EMDB-34825, PDB-8hip:
dsRNA transporter
Method: EM (single particle) / Resolution: 2.77 Å

34850

8hke

EMDB-34850, PDB-8hke:
dsRNA transporter
Method: EM (single particle) / Resolution: 3.71 Å

36008

8j6m

EMDB-36008, PDB-8j6m:
SIDT1 protein
Method: EM (single particle) / Resolution: 2.77 Å

36009

8j6o

EMDB-36009, PDB-8j6o:
transport T2
Method: EM (single particle) / Resolution: 3.25 Å

Chemicals

ChemComp-6OU:
[(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate / phospholipid*YM

ChemComp-ZN:
Unknown entry

ChemComp-CLR:
CHOLESTEROL / Cholesterol

ChemComp-NA:
Unknown entry

ChemComp-OLA:
OLEIC ACID / Oleic acid

ChemComp-HOH:
WATER / Water

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • homo sapiens (human)
  • aequorea victoria (jellyfish)
KeywordsRNA BINDING PROTEIN / dsRNA transporter / TRANSCRIPTION / transport T1 / TRANSPORT PROTEIN / transport T2

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