PKR Senses Nuclear and Mitochondrial Signals by Interacting with Endogenous Double-Stranded RNAs

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Protein kinase RNA-activated (PKR) induces immune response by sensing viral double-stranded RNAs (dsRNAs). However, growing evidence suggests that PKR can also be activated by endogenously expressed dsRNAs. Here, we capture these dsRNAs by formaldehyde-mediated crosslinking and immunoprecipitation sequencing and find that various noncoding RNAs interact with PKR. Surprisingly, the majority of the PKR-interacting RNA repertoire is occupied by mitochondrial RNAs (mtRNAs). MtRNAs can form intermolecular dsRNAs owing to bidirectional transcription of the mitochondrial genome and regulate PKR and eIF2 alpha phosphorylation to control cell signaling and translation. Moreover, PKR activation by mtRNAs is counteracted by PKR phosphatases, disruption of which causes apoptosis from PKR overactivation even in uninfected cells. Our work unveils dynamic regulation of PKR even without infection and establishes PKR as a sensor for nuclear and mitochondrial signaling cues in regulating cellular metabolism.
Publisher
CELL PRESS
Issue Date
2018-09
Language
English
Article Type
Article
Citation

MOLECULAR CELL, v.71, no.6, pp.1051 - +

ISSN
1097-2765
DOI
10.1016/j.molcel.2018.07.029
URI
http://hdl.handle.net/10203/246031
Appears in Collection
CBE-Journal Papers(저널논문)
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