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PKR senses nuclear and mitochondrial signals by interacting with endogenous double-stranded RNAs

Cited 39 time in Web of Science Cited 38 time in Scopus
Authors
Kim, Yoosik; Park, Joha; Kim, Sujin; Kim, MinA; Kang, Myeong-Gyun; Kwak, Chulhwan; Kang, Minjeong; Kim, Baekgyu; Rhee, Hyun-Woo; Kim, V. Narry
Issue Date
2018-09
Citation
Molecular Cell, Vol.71 No.6, pp.1051-1063.e6
Abstract
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.
ISSN
1097-2765
URI
https://hdl.handle.net/10371/171892
DOI
https://doi.org/10.1016/j.molcel.2018.07.029
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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