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| Status |
Public on Jul 18, 2018 |
| Title |
PKR senses nuclear and mitochondrial signals by interacting with endogenous double-stranded RNAs |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 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.
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| Overall design |
PKR fCLIP was performed on S and M phase arrested HeLa cells using PKR & J2 antibodies. Size-matched input samples are also collected and sequenced for each IP sample.
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| Contributor(s) |
Kim Y, Park J, Kim VN |
| Citation(s) |
30174290 |
| Submission date |
Jan 10, 2018 |
| Last update date |
Mar 27, 2019 |
| Contact name |
Joha Park |
| E-mail(s) |
johapark@gmail.com
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| Organization name |
Seoul National University
|
| Department |
Biological Sciences
|
| Street address |
1 Gwanak-ro, Gwanak-gu
|
| City |
Seoul |
| ZIP/Postal code |
08826 |
| Country |
South Korea |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL15520 |
Illumina MiSeq (Homo sapiens) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA429340 |
| SRA |
SRP128638 |
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