title: Specific and potent RNAi in the nucleus of human cells.
abstract: RNA interference (RNAi) has become a research tool to control gene expression in various organisms and holds potential as a new therapeutic strategy. The mechanism of small interfering RNA (siRNA)-mediated RNAi involves target mRNA cleavage and destruction in the cytoplasm. We investigated siRNA-mediated induction of RNAi in the nucleus of human cells. Notably, we observed highly efficient knockdown of small nuclear RNA 7SK by siRNA. siRNA- and microRNA-programmed RNA-induced silencing complexes (RISCs) were present in both cytoplasmic and nuclear compartments and specifically cleaved their perfectly matched target RNA with markedly high efficiencies. Our results provide the first evidence that human RISCs programmed with siRNA are present in the nucleus and can knock down target RNA levels. These studies reveal new roles for the RNAi machinery in modulating post-transcriptional gene expression in the nucleus.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: G Brett
authors.initials: GB
authors.lastname: Robb
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Brown
authors.forename: Jaspreet
authors.initials: J
authors.lastname: Khurana
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Rana
mesh_terms: D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012680:Sensitivity and Specificity; D013379:Substrate Specificity
chemical_list: D035683:MicroRNAs; D034741:RNA, Small Interfering