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

Molecular Cell
Yoosik KimV Narry Kim

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.

Citations

Jan 24, 2019·Annual Review of Immunology·Sun Hur
May 18, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Sujin KimYoosik Kim
Jun 25, 2019·Wiley Interdisciplinary Reviews. RNA·Yong Sun LeeYeon-Su Lee
Nov 16, 2019·Science·Sandra L Wolin, Lynne E Maquat
Nov 23, 2019·Wiley Interdisciplinary Reviews. RNA·Mariavittoria PizzingaAnne E Willis
Dec 22, 2019·Cells·Anna V Kotrys, Roman J Szczesny
Jun 3, 2020·Journal of Biochemistry·Ryan HoustonYusuke Sekine
Jan 29, 2019·Frontiers in Molecular Neuroscience·Shunit Gal-Ben-AriKobi Rosenblum
Jun 27, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Charles Bou-Nader, Jinwei Zhang
Sep 10, 2020·Viruses·Nina EiermannAlessia Ruggieri
Sep 5, 2019·Frontiers in Cardiovascular Medicine·Esam S B SalemTakahisa Nakamura
May 16, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Juan Felipe Valdés LópezSilvio Urcuqui-Inchima
Mar 18, 2019·BMC Biomedical Engineering·Ahsan Ausaf AliYoosik Kim
Jun 30, 2019·Nature Communications·Iris V HoodJinwei Zhang
Nov 22, 2019·Chemical Society Reviews·Toru ShimizuMarkéta Martínková
Jun 17, 2020·Science Advances·Jonathan P KastanMatthias Gromeier
Jun 1, 2019·Cell & Bioscience·Zhi-Ming Zheng
Mar 21, 2020·Advanced Science·Abdullah F U H SaeedSongying Ouyang
Jan 3, 2021·The FEBS Journal·Evelyn ChukwurahMaria Hatzoglou
Mar 7, 2021·Non-coding RNA·Shaymaa SadeqAndreas Werner
May 18, 2021·Frontiers in Aging Neuroscience·Nicolás W MartinezSoledad Matus
Jun 30, 2021·Molecular Medicine Reports·Viviane Aline Oliveira SilvaFernando Luiz De Lucca
Jul 14, 2021·Nature Cell Biology·Li-Sheng ZhangChuan He
Oct 15, 2020·Open Biology·Ananya HariharanEmanuela Felley-Bosco
Aug 28, 2021·International Journal of Molecular Sciences·Marta Luna-SánchezAlbert Quintana
Sep 1, 2021·Wiley Interdisciplinary Reviews. RNA·Alyssa M EnglishStephanie L Moon
Apr 2, 2021·Annual Review of Genomics and Human Genetics·Xiao-Ou ZhangZhiping Weng
Sep 10, 2021·Wiley Interdisciplinary Reviews. RNA·Joanna GrochowskaRoman J Szczesny
Jun 24, 2021·Genome Research·Andreas WernerJohn S Mattick

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