Article
Multidisciplinary Sciences
Keiichiro Nakamura, Kunitoshi Shigeyasu, Kazuhiro Okamoto, Hirofumi Matsuoka, Hisashi Masuyama
Summary: Adenosine deaminase acting on RNA 1 (ADAR1) is an epigenetic modifier and plays a critical oncogenic role in human cancers. Its functional role and clinical significance in cervical cancer (CC) were investigated. Knockdown of ADAR1 increased apoptosis and necroptosis in CC cell lines. High cytoplasmic and nuclear ADAR1 expression was associated with poorer prognosis in CC patients. ADAR1 could be a potential therapeutic target for HPV-positive or HPV-negative CC.
SCIENTIFIC REPORTS
(2023)
Article
Microbiology
Huiyi Li, Shun Liu, Qing Feng, Rilin Deng, Jingjing Wang, Xintao Wang, Renyun Tian, Yan Xu, Shengwen Chen, Qian Liu, Luoling Wang, Xinran Li, Mengyu Wan, Yousong Peng, Songqing Tang, Binbin Xue, Haizhen Zhu
Summary: The study reveals that TRIM21 negatively regulates the PKR-eIF2 alpha signaling pathway, providing new insights into the host antiviral response. TRIM21 promotes K6-linked polyubiquitination of the PKR phosphatase PP1 alpha, resulting in PKR dephosphorylation and release of translational inhibition. Furthermore, TRIM21 plays a role in restricting viral infection by reversing PKR-dependent translational inhibition of various antiviral factors.
Article
Multidisciplinary Sciences
Coralie Guy, Marcin Baran, Pau Ribo-Molina, Bernadette G. van den Hoogen, Andrew G. Bowie
Summary: This study reveals the mechanisms of viral sensing in human bronchial epithelial cells and demonstrates that poly(I:C) is sensed by NLRP1 and PKR pathways to activate caspases for cleavage of gasdermins. The study also highlights the antiviral role of gasdermin pore formation in human epithelial cells.
Article
Multidisciplinary Sciences
Li Guo, Cheng Hu, Yang Liu, Xiaoyu Chen, Deli Song, Runling Shen, Zhanzhen Liu, Xudong Jia, Qinfen Zhang, Yuanzhu Gao, Zhezhi Deng, Tao Zuo, Jun Hu, Wenbo Zhu, Jing Cai, Guangmei Yan, Jiankai Liang, Yuan Lin
Summary: Directed natural evolution is used to increase the oncolytic effect of the oncolytic virus M1 by inducing mutations in the E2 and nsP3 genes. The next-generation oncolytic virus generated, NGOVM, exhibits a broader antitumor spectrum and more robust oncolytic effect. This study demonstrates the potential of directed natural evolution in developing next-generation oncolytic viruses with increased effectiveness and safety.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Wen-Tao Sun, Cindy L. H. Yang, Terry C. T. Or, Dan Luo, James C. B. Li
Summary: Ginsenoside Rb1 has been found to inhibit the expression of MMP-9 and inflammatory response induced by tumor necrosis factor, suggesting its potential clinical applications in treating cardiac remodeling and liver cancer metastasis.
Article
Biochemistry & Molecular Biology
Luyao Wei, Wantao Wang, Junxia Yao, Zhengyu Cui, Zihang Xu, Hanqing Ding, Xiaojun Wu, Deheng Wang, Jia Luo, Zun-Ji Ke
Summary: This study identifies protein activator of the interferon-induced protein kinase (PACT) as a key player in basal-like breast cancer (BLBC) metastasis. High expression of PACT is associated with poor prognosis in BLBC patients. It is found that PACT regulates BLBC metastasis by interacting with SUMO-conjugating enzyme Ubc9.
Article
Multidisciplinary Sciences
Jiyoung Lee, Cristina Olivieri, Colin Ong, Larry R. Masterson, Suzana Gomes, Bok-Soon Lee, Florian Schaefer, Kristina Lorenz, Gianluigi Veglia, Marsha Rich Rosner
Summary: Phosphorylation of RKIP at S153 by PKC triggers a switch from inhibition of Raf to inhibition of GRK2, enhancing signaling by beta-AR that activates PKA. PKA-phosphorylated RKIP at S51 promotes beta-AR-activated PKA signaling by triggering feedback activation of PKA. This allosteric regulatory mechanism may have therapeutic potential for regulating PKA signaling in disease states.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Janani Parameswaran, Nancy Zhang, Elke Braems, Kedamawit Tilahun, Devesh C. Pant, Keena Yin, Seneshaw Asress, Kara Heeren, Anwesha Banerjee, Emma Davis, Samantha L. Schwartz, Graeme L. Conn, Gary J. Bassell, Ludo van den Bosch, Jie Jiang
Summary: GGGGCC (G(4)C(2)) repeat expansion in C9ORF72 gene is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Our study shows that C9ORF72 antisense C(4)G(2) repeat expanded RNAs activate the PKR/eIF2a-dependent integrated stress response, leading to translation inhibition and stress granule formation. PKR levels reduction mitigates stress response and toxicity caused by the antisense C(4)G(2) RNAs. Increased phosphorylation of PKR/eIF2a is also observed in the frontal cortex of C9ORF72 FTD/ALS patients. Only antisense C(4)G(2) repeat expanded RNAs activate the PKR/eIF2a pathway and induce aberrant stress granule formation.
Article
Microbiology
Zekun Wang, Songyang Ren, Qiming Li, Austin D. Royster, Lei Lin, Sichen Liu, Safder S. Ganaie, Jianming Qiu, Sheema Mir, Mohammad A. Mir
Summary: The Hantavirus nucleocapsid protein (NP) inhibits protein kinase R (PKR) by using an endogenous PKR inhibitor P58(IPK) to compete with its negative regulator Hsp40, releasing P58(IPK) and selectively engaging it on the 40S ribosomal subunit.
Article
Biochemistry & Molecular Biology
Rebeka Popovic, Ivana Celardo, Yizhou Yu, Ana C. Costa, Samantha H. Y. Loh, L. Miguel Martins
Summary: In Drosophila, activation of dPerk by ER stress or defective mitochondria plays a role in neurodegenerative disorders. The study showed that dPerk activation leads to translational repression of mitochondrial proteins associated with various metabolic and signaling pathways. Further enhancing translation of these targets may offer protection against Perk toxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Max Paget, Cristhian Cadena, Sadeem Ahmad, Hai-Tao Wang, Tristan X. Jordan, Ehyun Kim, Beechui Koo, Shawn M. Lyons, Pavel Ivanov, Benjamin tenOever, Xin Mu, Sun Hur
Summary: Proper defense against microbial infection relies on controlled activation of the immune system, especially for RIG-I-like receptors (RLRs) recognizing viral dsRNA. Stress granules (SGs) play critical roles in regulating RLR signaling, preventing excessive inflammation and immune-mediated apoptosis. SGs also have the ability to suppress viral replication independently of the RLR pathway, demonstrating their multi-functional nature as cellular shock absorbers for maintaining cell homeostasis.
Article
Biochemistry & Molecular Biology
Katarzyna Taylor, Agnieszka Piasecka, Arkadiusz Kajdasz, Aleksandra Brzek, Micaela Polay Espinoza, Cyril F. Bourgeois, Artur Jankowski, Malgorzata Borowiak, Katarzyna D. Raczynska, Lukasz J. Sznajder, Krzysztof Sobczak
Summary: This study aims to elucidate the mechanism of muscleblind-like splicing regulators (MBNLs) in alternative splicing (AS) processes. The findings indicate that DEAD-box (DDX) RNA helicases DDX5 and DDX17 play an important role in MBNL-dependent AS regulation. The helicases modulate MBNL splicing activity through changes in the ratio of MBNL splicing isoforms and accessibility of MBNL-binding sites. These findings contribute to a deeper understanding of the interdependencies between RNA-binding proteins and their implications in developmental homeostasis and pathological states.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Microbiology
Thomas C. Montavon, Morgane Baldaccini, Mathieu Lefevre, Erika Girardi, Beatrice Chane-Woon-Ming, Melanie Messmer, Philippe Hammann, Johana Chicher, Sebastien Pfeffer
Summary: This study investigates the role of DICER in human cells infected with alphaviruses and reveals its interaction with various proteins, potentially linking to RNA silencing and type I interferon antiviral responses. The N-terminal helicase domain of DICER acts as a platform to recruit RNA binding proteins during infection, conferring antiviral activity to DICER.
Article
Microbiology
Bo Gao, Xiaoqian Gong, Shouguo Fang, Wenlian Weng, Huan Wang, Hongyan Chu, Yingjie Sun, Chunchun Meng, Lei Tan, Cuiping Song, Xusheng Qiu, Weiwei Liu, Maria Forlenza, Chan Ding, Ying Liao
Summary: Coronaviruses use the endoribonuclease nsp15 to interfere with the formation of anti-viral stress granules (SGs), reducing viral dsRNA accumulation and antagonizing PKR activation, thereby ensuring productive virus replication. Nsp15s from various coronaviruses interfere with SGs formation, possibly by targeting essential SGs assembly factors, indicating a conserved mechanism among coronaviruses to counteract host antiviral responses. This study highlights the role of nsp15 in suppressing the integral stress response and crosstalk with anti-innate immune response.
Article
Cell Biology
Jiaying Huang, Zhou Yu, Xuelian Li, Mingjin Yang, Qian Fang, Zheng Li, Chunmei Wang, Taoyong Chen, Xuetao Cao
Summary: Uncontrolled viral replication and excessive inflammation are the main causes of death in virus-infected hosts. The E3 ligase HECTD3 plays a role in regulating virus replication and innate cytokine production. Deficiency of HECTD3 accelerates virus clearance and reduces inflammatory response by disrupting the dimerization and phosphorylation of dsRNA-dependent protein kinase R (PKR) and subsequent EIF2α activation. HECTD3 is a potential therapeutic target for restraining virus replication and virus-induced inflammation.
CELL DEATH & DISEASE
(2023)