The current SARS-CoV-2 pandemic has spurred new interest in interferon signaling in response to viral pathogens. Much of what we know about the signaling molecules and associated signal transduction induced during the host cellular response to viral pathogens has been gained from research conducted from the 1990's to the present day, but certain intricacies of the mechanisms involved, still remain unclear. In a recent study by Vaughn et al. the authors examine one of the main mechanisms regulating interferon induction following viral infection, the RIG-I/MAVS/IRF3 pathway, and find that similar to PKR both DICER interacting proteins, PACT and TRBP, regulate RIG-I signaling in an opposing manner. More specifically, the reported findings demonstrate, like others, that PACT stimulates RIG-I-mediated signaling in a manner independent of PACT dsRNA-binding ability or phosphorylation at sites known to be important for PACT-dependent PKR activation. In contrast, they show for the first time that TRBP inhibits RIG-I-mediated signaling. RIG-I inhibition by TRBP did not require phosphorylation of sites shown to be important for inhibiting PKR, nor did it involve PACT or PKR, but it did require the dsRNA-binding ability of TRBP. These findings open the door to a complex co-regulation of RIG-I, PKR, MDA5, miRNA processing, and interferon induction.
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May 2021
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Amphisomes are intermediate/hybrid organelles produced through the fusion of endosomes with autophagosomes within cells. In this issue Ganesan and Cai (pp. 1959–1976) provide an updated overview of the recent discoveries and advancements on the molecular and cellular mechanisms underlying amphisome biogenesis and the emerging roles of amphisomes. The image shows amphisome retrograde transport in the axons of neurons. Image courtesy of Qian Cai.
Commentary|
May 18 2021
Opposing forces fight over the same ground to regulate interferon signaling
William L. Blalock
1‘Luigi Luca Cavalli-Sforza’ Istituto di Genetica Molecolare-Consiglio Nazionale delle Ricerche (IGM-CNR), Bologna, Italy
2IRCCS, Istituto Ortopedico Rizzoli, Bologna, Italy
Correspondence: William L. Blalock (william.blalock@cnr.it)
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Publisher: Portland Press Ltd
Received:
March 19 2021
Revision Received:
April 20 2021
Accepted:
April 22 2021
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2021
Biochem J (2021) 478 (10): 1853–1859.
Article history
Received:
March 19 2021
Revision Received:
April 20 2021
Accepted:
April 22 2021
Connected Content
This is a commentary on:
Opposite actions of two dsRNA-binding proteins PACT and TRBP on RIG-I mediated signaling
Citation
William L. Blalock; Opposing forces fight over the same ground to regulate interferon signaling. Biochem J 28 May 2021; 478 (10): 1853–1859. doi: https://doi.org/10.1042/BCJ20210110
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