2015
DOI: 10.1073/pnas.1513034112
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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 aff… Show more

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Cited by 45 publications
(54 citation statements)
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“…Our results, consistent with other published data [21,22], shows that prostate cancer cells depleted of RNase L show greater migration in wound healing and transwell migration assays in response to fibronectin and serum (Figure 5). In reconstitution experiments, over-expression of RNase L suppressed cell migration compared to both endogenous levels and knockdown cells while activation of RNase L, which requires RNase L dimerization, inhibited cell migration (Figure 6).…”
Section: Discussionsupporting
confidence: 93%
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“…Our results, consistent with other published data [21,22], shows that prostate cancer cells depleted of RNase L show greater migration in wound healing and transwell migration assays in response to fibronectin and serum (Figure 5). In reconstitution experiments, over-expression of RNase L suppressed cell migration compared to both endogenous levels and knockdown cells while activation of RNase L, which requires RNase L dimerization, inhibited cell migration (Figure 6).…”
Section: Discussionsupporting
confidence: 93%
“…RNase L also inhibits cell attachment to ECM substrates and cell spreading on fibronectin. An earlier report showed that activity of RNase L downregulates transcripts involved in cell adhesion both transcriptionally and post-transcriptionally [22]. In contrast, we observed the suppressive effect of RNase L on cell migration in cells expressing endogenous RNase L in the absence of activation or with mutants that lacked enzyme activity.…”
Section: Discussioncontrasting
confidence: 74%
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“…RNase L protects from pathogens and controls cell growth and differentiation by disrupting largely unidentified mammalian RNA targets. Rath et al (2015) revealed that RNase L-dependent decay selectively disturbs transcripts controlled by microRNA (miR)-17/miR-29/miR-200 and other miRs that function as suppressors of mammalian cell adhesion and multiplication. RNase L acts as a suppressor of proliferation and adhesion in mammalian cells.…”
Section: Introductionmentioning
confidence: 99%
“…RNase L acts as a suppressor of proliferation and adhesion in mammalian cells. Rath et al (2015) concluded that RNase L-dependent decay starts an anti-proliferative state via disruption of the miR-controlled transcriptome.…”
Section: Introductionmentioning
confidence: 99%