Visualizing a correlation between siRNA localization, cellular uptake, and RNAi in living cells
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UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyGraduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2004-08-25Keywords
Base Sequence; Biopolymers; Carbamates; Cell Survival; Cyclin-Dependent Kinase 9; Cytoplasm; Gene Products, tat; Hela Cells; Humans; Molecular Sequence Data; Nanostructures; Peptide Fragments; *RNA Interference; *RNA Transport; RNA, Small InterferingLife Sciences
Medicine and Health Sciences
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Show full item recordAbstract
RNA interference (RNAi) is the process by which short-interfering RNA (siRNA) target a specific mRNA for degradation through interactions with an RNA-induced silencing complex (RISC). Here, a clear correlation between siRNA localization, cellular uptake, and RNAi activity was discovered by delivering siRNA into cells using siRNA-TAT(47-57) peptide, siRNA-TAT(47-57)-derived oligocarbamate conjugates, or nanoparticles. For successful RNAi, the localization of siRNA was distinctly perinuclear, suggesting that siRNA is targeted to these regions for interactions with RISC to induce RNAi. siRNA sequence variation and the presence of the target mRNA apparently did not change the subcellular localization pattern of siRNA. Intriguingly, siRNA conjugated to TAT(47-57) peptide or TAT(47-57)-derived oligocarbamate resulted in efficient RNAi activity and perinuclear localization of siRNA that was distinctly different from nonconjugated free TAT peptide nucleolar localization. These results suggest that interactions with RISC dictate siRNA localization even when siRNA is conjugated to TAT(47-57) peptide.Source
Chem Biol. 2004 Aug;11(8):1165-75. Link to article on publisher's siteDOI
10.1016/j.chembiol.2004.06.006Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33534PubMed ID
15324818Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.chembiol.2004.06.006