title: MicroRNAs can generate thresholds in target gene expression.
abstract: MicroRNAs (miRNAs) are short, highly conserved noncoding RNA molecules that repress gene expression in a sequence-dependent manner. We performed single-cell measurements using quantitative fluorescence microscopy and flow cytometry to monitor a target gene's protein expression in the presence and absence of regulation by miRNA. We find that although the average level of repression is modest, in agreement with previous population-based measurements, the repression among individual cells varies dramatically. In particular, we show that regulation by miRNAs establishes a threshold level of target mRNA below which protein production is highly repressed. Near this threshold, protein expression responds sensitively to target mRNA input, consistent with a mathematical model of molecular titration. These results show that miRNAs can act both as a switch and as a fine-tuner of gene expression.
authors.affiliation: Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Shankar
authors.initials: S
authors.lastname: Mukherji
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Ebert
authors.forename: Grace X Y
authors.initials: GX
authors.lastname: Zheng
authors.forename: John S
authors.initials: JS
authors.lastname: Tsang
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Sharp
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
mesh_terms: D001665:Binding Sites; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation; D018390:Gene Targeting; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D008856:Microscopy, Fluorescence
chemical_list: D035683:MicroRNAs; D008156:Luciferases