title: Human RNase L tunes gene expression by selectively destabilizing the microRNA-regulated transcriptome.
abstract: Double-stranded RNA (dsRNA) activates the innate immune system of mammalian cells and triggers intracellular RNA decay by the pseudokinase and endoribonuclease RNase L. RNase L protects from pathogens and regulates cell growth and differentiation by destabilizing largely unknown mammalian RNA targets. We developed an approach for transcriptome-wide profiling of RNase L activity in human cells and identified hundreds of direct RNA targets and nontargets. We show that this RNase L-dependent decay selectively affects transcripts regulated by microRNA (miR)-17/miR-29/miR-200 and other miRs that function as suppressors of mammalian cell adhesion and proliferation. RNase L mimics the effects of these miRs and acts as a suppressor of proliferation and adhesion in mammalian cells. Our data suggest that RNase L-dependent decay serves to establish an antiproliferative state via destabilization of the miR-regulated transcriptome.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544;
authors.forename: Sneha
authors.initials: S
authors.lastname: Rath
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544;
authors.forename: Jesse
authors.initials: J
authors.lastname: Donovan
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544;
authors.forename: Gena
authors.initials: G
authors.lastname: Whitney
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544;
authors.forename: Alisha
authors.initials: A
authors.lastname: Chitrakar
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544; Sequencing Core Facility, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544; akorenny@princeton.edu.
authors.forename: Alexei
authors.initials: A
authors.lastname: Korennykh
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D004722:Endoribonucleases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: C524941:MIRN17 microRNA, human; C533896:MIRN200 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease
keywords: RNase L; adhesion; dsRNA; miR-200; microRNA