skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein

Abstract

Highlights: •TRK-fused gene product (TFG) interacts with TRIM25 upon viral infection. •TFG negatively regulates RIG-I mediated antiviral signaling. •TFG depletion leads to enhanced viral replication. •TFG act downstream of MAVS. -- Abstract: RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediated IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways.

Authors:
; ; ; ;
Publication Date:
OSTI Identifier:
22239679
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 437; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; GENES; INHIBITION; INTERFERON; MITOCHONDRIA; RECEPTORS; RETINOIC ACID; RNA; VIRUSES

Citation Formats

Lee, Na-Rae, Shin, Han-Bo, Kim, Hye-In, Choi, Myung-Soo, and Inn, Kyung-Soo. Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein. United States: N. p., 2013. Web. doi:10.1016/J.BBRC.2013.06.061.
Lee, Na-Rae, Shin, Han-Bo, Kim, Hye-In, Choi, Myung-Soo, & Inn, Kyung-Soo. Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein. United States. https://doi.org/10.1016/J.BBRC.2013.06.061
Lee, Na-Rae, Shin, Han-Bo, Kim, Hye-In, Choi, Myung-Soo, and Inn, Kyung-Soo. 2013. "Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein". United States. https://doi.org/10.1016/J.BBRC.2013.06.061.
@article{osti_22239679,
title = {Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein},
author = {Lee, Na-Rae and Shin, Han-Bo and Kim, Hye-In and Choi, Myung-Soo and Inn, Kyung-Soo},
abstractNote = {Highlights: •TRK-fused gene product (TFG) interacts with TRIM25 upon viral infection. •TFG negatively regulates RIG-I mediated antiviral signaling. •TFG depletion leads to enhanced viral replication. •TFG act downstream of MAVS. -- Abstract: RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediated IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways.},
doi = {10.1016/J.BBRC.2013.06.061},
url = {https://www.osti.gov/biblio/22239679}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 437,
place = {United States},
year = {Fri Jul 19 00:00:00 EDT 2013},
month = {Fri Jul 19 00:00:00 EDT 2013}
}