title: A small molecule enhances RNA interference and promotes microRNA processing.
abstract: Small interfering RNAs (siRNAs) and microRNAs (miRNAs) are sequence-specific post-transcriptional regulators of gene expression. Although major components of the RNA interference (RNAi) pathway have been identified, regulatory mechanisms for this pathway remain largely unknown. Here we demonstrate that the RNAi pathway can be modulated intracellularly by small molecules. We have developed a cell-based assay to monitor the activity of the RNAi pathway and find that the small-molecule enoxacin (Penetrex) enhances siRNA-mediated mRNA degradation and promotes the biogenesis of endogenous miRNAs. We show that this RNAi-enhancing activity depends on the trans-activation-responsive region RNA-binding protein. Our results provide a proof-of-principle demonstration that small molecules can be used to modulate the activity of the RNAi pathway. RNAi enhancers may be useful in the development of research tools and therapeutics.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, 615 Michael St, Atlanta, Georgia 30322, USA.
authors.forename: Ge
authors.initials: G
authors.lastname: Shan
authors.forename: Yujing
authors.initials: Y
authors.lastname: Li
authors.forename: Junliang
authors.initials: J
authors.lastname: Zhang
authors.forename: Wendi
authors.initials: W
authors.lastname: Li
authors.forename: Keith E
authors.initials: KE
authors.lastname: Szulwach
authors.forename: Ranhui
authors.initials: R
authors.lastname: Duan
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Faghihi
authors.forename: Ahmad M
authors.initials: AM
authors.lastname: Khalil
authors.forename: Lianghua
authors.initials: L
authors.lastname: Lu
authors.forename: Zain
authors.initials: Z
authors.lastname: Paroo
authors.forename: Anthony W S
authors.initials: AW
authors.lastname: Chan
authors.forename: Zhangjie
authors.initials: Z
authors.lastname: Shi
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Liu
authors.forename: Claes
authors.initials: C
authors.lastname: Wahlestedt
authors.forename: Chuan
authors.initials: C
authors.lastname: He
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
mesh_terms: D000818:Animals; D002460:Cell Line; D015365:Enoxacin / Q000494:pharmacology*; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference / Q000187:drug effects*; D012323:RNA Processing, Post-Transcriptional; D034741:RNA, Small Interfering / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D014162:Transfection; D000099253:Trans-Activation Responsive RNA-Binding Protein
chemical_list: D015365:Enoxacin; D049452:Green Fluorescent Proteins; D035683:MicroRNAs; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; D000099253:Trans-Activation Responsive RNA-Binding Protein; C485184:enhanced green fluorescent protein