PKR binds activating host RNA

Stable Identifier
R-HSA-9833777
Type
Reaction [binding]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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RNA is the primary regulator of PKR (EIF2AK2) and this regulation can be either activating, inhibiting, or neutral. Types of RNA binding to PKR include ssRNA (Mayo et al., 2016), dsRNA (Patel et al., 1996), short double-stranded RNAs with single-stranded tails (ss-dsRNA), small nucleolar RNA (snoRNA)(Youssef et al, 2015), circular RNA (Liu et al, 2019), and nascent (unmodified) tRNA (reviewed by Dauber & Wolff, 2009; Hull & Bevilacqua, 2016; Bou-Nader et al, 2019). Efflux of mitochondrial RNA (mtRNA) to the cytosol activates PKR in osteoarthritis (Kim et al, 2018; Kim et al, 2022). RNA binds to one or both of the two double-stranded RNA-binding motifs (dsRBMs) of PKR (Meurs et al, 1990; Patel & Sen, 1992; Patel & Sen, 1998; Zhang et al, 2001; reviewed by Bou-Nader et al, 2019). This interaction, and the following recruitment of PKR to stress granules, is facilitated by the MAVS protein (Zhang et al, 2014).
Literature References
PubMed ID Title Journal Year
11337501 Binding of double-stranded RNA to protein kinase PKR is required for dimerization and promotes critical autophosphorylation events in the activation loop

Dever, TE, Tian, B, Hinnebusch, AG, Romano, PR, Mathews, MB, Zhang, F, Nagamura-Inoue, T, Ozato, K

J Biol Chem 2001
21994559 Activation of the Antiviral Kinase PKR and Viral Countermeasures

Dauber, B, Wolff, T

Viruses 2009
25848059 Potential role for snoRNAs in PKR activation during metabolic stress

Youssef, OA, Nix, DA, Bass, BL, Safran, SA, Nakamura, T, Hotamisligil, GS

Proc Natl Acad Sci U S A 2015
30770398 The search for a PKR code-differential regulation of protein kinase R activity by diverse RNA and protein regulators

Gordon, JM, Bou-Nader, C, Henderson, FE, Zhang, J

RNA 2019
1373135 Identification of the double-stranded RNA-binding domain of the human interferon-inducible protein kinase

Patel, RC, Sen, GC

J Biol Chem 1992
24659800 IPS-1 plays an essential role in dsRNA-induced stress granule formation by interacting with PKR and promoting its activation

Pu, J, Li, Y, Wu, S, Xia, J, Huang, X, Zhang, P, Zhang, P, He, J, Feng, L, Xie, J

J Cell Sci 2014
1695551 Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon

Hovanessian, AG, Thomas, NS, Williams, BR, Galabru, J, Meurs, E, Kerr, IM, Chong, K

Cell 1990
30174290 PKR Senses Nuclear and Mitochondrial Signals by Interacting with Endogenous Double-Stranded RNAs

Park, J, Rhee, HW, Kang, MG, Kim, M, Kim, Y, Kim, B, Kim, S, Kwak, C, Kim, VN, Kang, M

Mol Cell 2018
31031002 Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity

Guo, SK, Chen, LL, Dong, K, Xue, W, Gao, X, Nan, F, Cui, Y, Shen, N, Yang, L, Jiang, S, Qu, B, Ding, H, Li, X, Zhou, Z, Liu, CX

Cell 2019
27269119 Discriminating Self and Non-Self by RNA: Roles for RNA Structure, Misfolding, and Modification in Regulating the Innate Immune Sensor PKR

Bevilacqua, PC, Hull, CM

Acc Chem Res 2016
9819388 Requirement of PKR dimerization mediated by specific hydrophobic residues for its activation by double-stranded RNA and its antigrowth effects in yeast

Patel, RC, Sen, GC

Mol Cell Biol 1998
8810342 Specific mutations near the amino terminus of double-stranded RNA-dependent protein kinase (PKR) differentially affect its double-stranded RNA binding and dimerization properties

Patel, RC, Stanton, P, Sen, GC

J Biol Chem 1996
35947956 Mitochondrial double-stranded RNAs govern the stress response in chondrocytes to promote osteoarthritis development

Yoon, J, Lee, YJ, Kharbash, R, Lee, YS, Kim, Y, Choi, YS, Ku, J, Kim, H, Lee, K, Kim, S, Kim, JH

Cell Rep 2022
27208315 Activation of PKR by short stem-loop RNAs containing single-stranded arms

Lary, JW, Cole, JL, Mayo, CB, Lopez, PE, Wong, CJ

RNA 2016
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