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 eIF2α 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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Kim Y,Park J,Kim S,Kim M,Kang MG,Kwak C,Kang M,Kim B,Rhee HW,Kim VNdoi
10.1016/j.molcel.2018.07.029subject
Has Abstractpub_date
2018-09-20 00:00:00pages
1051-1063.e6issue
6eissn
1097-2765issn
1097-4164pii
S1097-2765(18)30598-7journal_volume
71pub_type
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