Structural insights into double-stranded RNA recognition and transport by SID-1.
Nat Struct Mol Biol
; 31(7): 1095-1104, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38664565
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 (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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA de Cadeia Dupla
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Caenorhabditis elegans
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Microscopia Crioeletrônica
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Proteínas de Caenorhabditis elegans
Limite:
Animals
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Humans
Idioma:
En
Revista:
Nat Struct Mol Biol
Ano de publicação:
2024
Tipo de documento:
Article