T-Cell Intracellular Antigen 1-Like Protein in Physiology and Pathology

Velasco, Beatriz Ramos; Izquierdo, José M.

doi:10.3390/ijms23147836

Cited by 10 publications

(9 citation statements)

References 169 publications

(350 reference statements)

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“…At the same time, how mRNA degradation stimulated by CoV2 or SARS Nsp1 results in nuclear accumulation of TIAR is less clear. TIAR is an RNA binding protein with 3 RNA recognition motifs (RRM1-3) and an auxiliary C-terminal domain that is involved in many stages of the mRNA life cycle, from transcription and splicing to translation and stability [ 83 ]. It was shown that nuclear import of TIAR is dependent on transcription of new pre-mRNAs and requires ATP hydrolysis and the RRM2 RNA-binding activity, and that the inhibition of RNA synthesis by ActD causes egress of TIAR from the nucleus into the cytoplasm [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

Nsp1 proteins of human coronaviruses HCoV-OC43 and SARS-CoV2 inhibit stress granule formation

et al. 2022

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Stress granules (SGs) are cytoplasmic condensates that often form as part of the cellular antiviral response. Despite the growing interest in understanding the interplay between SGs and other biological condensates and viral replication, the role of SG formation during coronavirus infection remains poorly understood. Several proteins from different coronaviruses have been shown to suppress SG formation upon overexpression, but there are only a handful of studies analyzing SG formation in coronavirus-infected cells. To better understand SG inhibition by coronaviruses, we analyzed SG formation during infection with the human common cold coronavirus OC43 (HCoV-OC43) and the pandemic SARS-CoV2. We did not observe SG induction in infected cells and both viruses inhibited eukaryotic translation initiation factor 2α (eIF2α) phosphorylation and SG formation induced by exogenous stress. Furthermore, in SARS-CoV2 infected cells we observed a sharp decrease in the levels of SG-nucleating protein G3BP1. Ectopic overexpression of nucleocapsid (N) and non-structural protein 1 (Nsp1) from both HCoV-OC43 and SARS-CoV2 inhibited SG formation. The Nsp1 proteins of both viruses inhibited arsenite-induced eIF2α phosphorylation, and the Nsp1 of SARS-CoV2 alone was sufficient to cause a decrease in G3BP1 levels. This phenotype was dependent on the depletion of cytoplasmic mRNA mediated by Nsp1 and associated with nuclear accumulation of the SG-nucleating protein TIAR. To test the role of G3BP1 in coronavirus replication, we infected cells overexpressing EGFP-tagged G3BP1 with HCoV-OC43 and observed a significant decrease in virus replication compared to control cells expressing EGFP. The antiviral role of G3BP1 and the existence of multiple SG suppression mechanisms that are conserved between HCoV-OC43 and SARS-CoV2 suggest that SG formation may represent an important antiviral host defense that coronaviruses target to ensure efficient replication.

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Section: Discussionmentioning

confidence: 99%

Nsp1 proteins of human coronaviruses HCoV-OC43 and SARS-CoV2 inhibit stress granule formation

et al. 2022

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“…In addition, keywords related to cytotoxicity, T-lymphocytes, viral infections (including Epstein–Barr Virus/herpesvirus 4) and immune response mechanisms are shared in the cluster, highlighting their importance in immune-related functions and surveillance and viral pathways. Collectively, these findings demonstrate that both proteins contribute to the regulation of cytotoxic T-lymphocytes, which are critical for immune responses against viruses and cancers [ 4 , 6 , 36 ], including lymphoma.…”

Section: Tia1- and Tiar-related Networking Analysismentioning

confidence: 99%

“…In the case of TIAR, its involvement has been reported in inflammation, embryogenesis, carcinogenesis and neurodegenerative diseases such as neurofibromatosis type I, axon regeneration and Alzheimer’s disease [ 6 ].…”

Section: Implications Of Tia1 and Tiar In Human Pathologiesmentioning

confidence: 99%

“…Although both proteins are widely expressed in human tissues, their distribution differs. TIA1 is highly expressed in the kidney and gonads, with significant expression in the small intestine, lung, skeletal muscle and pancreas [ 4 ], whereas TIAR is predominantly expressed in the brain and skeletal muscle, with lower expression in the heart, kidney and lung [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Bibliometric Overview on T-Cell Intracellular Antigens and Their Pathological Implications

Ramos-Velasco,

Naranjo,

Izquierdo

2024

Biology

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T-cell intracellular antigen 1 (TIA1) and TIA1-like/related protein (TIAL1/TIAR) are two members of the classical family of RNA binding proteins. Through their selective interactions with distinct RNAs and proteins, these multifunctional regulators are involved in chromatin remodeling, RNA splicing and processing and translation regulation, linking them to a wide range of diseases including neuronal disorders, cancer and other pathologies. From their discovery to the present day, many studies have focused on the behavior of these proteins in order to understand their impact on molecular and cellular processes and to understand their relationship to human pathologies. The volume of research on these proteins in various fields, including molecular biology, biochemistry, cell biology, immunology and cancer, has steadily increased, indicating a growing interest in these gene expression regulators among researchers. This information can be used to know the most productive institutions working in the field, understand the focus of research, identify key areas of involvement, delve deeper into their relationship and impact on different diseases, and to establish the level of study associated with them.

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“…For example, WNV produces its own RNA using TIA proteins. Furthermore, it is well known that Tick-borne encephalitis virus (TBEV) binds to viral replication sites via TIA-1 to regulate viral replication independently of the formation of stress granules (SGs) [37].…”

Section: Analysis Of the First Motif (Red Motif)mentioning

confidence: 99%

The Continuous Adaptive Challenge Played by Arboviruses: An <em>In Silico </em>Approach to Define Relevant Molecular Interactions with the Host

Chetta¹,

Cammarota²,

Marco³

et al. 2023

Preprint

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Climate change and globalization have raised the risk of vector-borne disease (VBD) introduction and spread in various European nations in recent years. In Italy, viruses carried by tropical vectors have been shown to cause viral encephalitis, one of the symptoms of arbovirosis, a spectrum of viral disorders spread by arthropods such as mosquitoes and ticks. Arbovirosis are currently causing alarm and attention, and the World Health Organization (WHO) has released recommendations to adopt essential measures, particularly during the hot season, to restrict the spreading of the infectious agents among breeding stocks. In this scenario, rapid analysis systems are required, because they can quickly provide information on potential virus-host interactions, the evolution of the infection, and the onset of disabling clinical symptoms, or serious illnesses. Such systems include bioinformatics approaches integrated with molecular evaluation. Viruses have co-evolved different strategies to transcribe their own genetic material, by changing the host's transcriptional machinery, even in short periods of time. The introduction of genetic alterations, particularly in RNA viruses, results in a continuous adaptive fight against the host's immune system. We suggest an in silico pipeline method to unravel viral sequences that may interact with host RNA binding proteins (RBPs), which play important roles in RNA metabolism and its several related biological processes. Indeed, viral RNA sequences, able to bind host RBPs may compete with cellular RNAs, altering important metabolic processes. Our findings suggest that the proposed in silico approach, could be a useful and promising tool to investigate the complex and multiform clinical manifestations of viral encephalitis, and possibly identify altered metabolic pathways as targets of pharmacological treatments and innovative therapeutic protocols.

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T-Cell Intracellular Antigen 1-Like Protein in Physiology and Pathology

Cited by 10 publications

References 169 publications

Nsp1 proteins of human coronaviruses HCoV-OC43 and SARS-CoV2 inhibit stress granule formation

Nsp1 proteins of human coronaviruses HCoV-OC43 and SARS-CoV2 inhibit stress granule formation

Bibliometric Overview on T-Cell Intracellular Antigens and Their Pathological Implications

The Continuous Adaptive Challenge Played by Arboviruses: An <em>In Silico </em>Approach to Define Relevant Molecular Interactions with the Host

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