studying-rna-interactors-protein-kinase-rna-activated-during

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle

Protein kinase RNA-activated (PKR) is a member of the innate immune response proteins and recognizes the double-stranded secondary structure of viral ...

Korea Advanced Institute of Science and Technology (KAIST)

Biomolecular regulatory networks are organised around hubs, which can interact with a large number of targets. These targets compete with each other for access to their common hubs, but whether the effect of this competition would be significant in magnitude and in function is not clear. In this review, the authors discuss recent  studies that analysed the system level retroactive effects induced by target competition in microRNA and mitogen-activated protein kinase regulatory networks. The results of these studies suggest that downstream targets can regulate the overall state of their upstream regulators, and thus cannot be ignored in analysing biomolecular networks.

Two faces of competition: target-mediated reverse signalling in microRNA and mitogen-activated protein kinase regulatory networks.

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.

Article	Year
Two faces of competition: target-mediated reverse signalling in microRNA and mitogen-activated protein kinase regulatory networks. IET systems biology\| PubMed ID: 28721939	2017
PKR Senses Nuclear and Mitochondrial Signals by Interacting with Endogenous Double-Stranded RNAs. Molecular cell\| PubMed ID: 30174290	2018

Yoosik Kim

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