8hip
From Proteopedia
dsRNA transporter
Structural highlights
FunctionSID1_CAEEL Plays a role in RNA-mediated gene silencing by acting cell-autonomously as a channel for the transport of double-stranded RNA (dsRNA) between cells. Mediates the spread of dsRNA and subsequent silencing of genes in cells distant from the site of dsRNA introduction. Selective for dsRNA. Preferentially binds long dsRNA, from 50 base pairs up to 700. Short 20 base-pair long molecules are not bound. May also bind dsDNA, but with lower affinity. Binding may be sequence-independent (PubMed:26067272). Required for avoidance behavior induced by small RNAs derived from pathogenic bacteria such as P.aeruginosa (PubMed:32908307).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] Publication Abstract from PubMedRNA 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. Structural insights into double-stranded RNA recognition and transport by SID-1.,Zhang J, Zhan C, Fan J, Wu D, Zhang R, Wu D, Chen X, Lu Y, Li M, Lin M, Gong J, Jiang D Nat Struct Mol Biol. 2024 Jul;31(7):1095-1104. doi: 10.1038/s41594-024-01276-9. , Epub 2024 Apr 25. PMID:38664565[14] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations No citations found References
|
|