The Regulatory Role of RNA Metabolism Regulator TDP-43 in Human Cancer

Ma, Xueyou; Ying, Yufan; Xie, Haiyun; Liu, Xiaoyan; Wang, Xiao; Li, Jiangfeng

doi:10.3389/fonc.2021.755096

Cited by 15 publications

(18 citation statements)

References 96 publications

(106 reference statements)

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“…Transactive response DNA-binding protein (TARDBP), also known as transactive response DNA binding protein 43 kDa (TDP-43), is a nuclear RNA-binding protein that is able to process RNA, thereby acting in different biological processes, including splicing, transcription and translation, mRNA transport, mRNA stability and pri-miRNA processing [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Since TDP-43 recognizes UG-rich sequences present within approximately one-third of all transcribed genes [ 5 , 6 , 10 ], it is uniquely able to influence the processing of hundreds to thousands of transcripts.…”

Section: Introductionmentioning

confidence: 99%

Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6

Cabrera-Rodríguez

Pérez-Yanes

González-Montelongo

et al. 2022

IJMS

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The transactive response DNA-binding protein (TARDBP/TDP-43) influences the processing of diverse transcripts, including that of histone deacetylase 6 (HDAC6). Here, we assessed TDP-43 activity in terms of regulating CD4+ T-cell permissivity to HIV-1 infection. We observed that overexpression of wt-TDP-43 increased both mRNA and protein levels of HDAC6, resulting in impaired HIV-1 infection independently of the viral envelope glycoprotein complex (Env) tropism. Consistently, using an HIV-1 Env-mediated cell-to-cell fusion model, the overexpression of TDP-43 levels negatively affected viral Env fusion capacity. Silencing of endogenous TDP-43 significantly decreased HDAC6 levels and increased the fusogenic and infection activities of the HIV-1 Env. Using pseudovirus bearing primary viral Envs from HIV-1 individuals, overexpression of wt-TDP-43 strongly reduced the infection activity of Envs from viremic non-progressors (VNP) and rapid progressors (RP) patients down to the levels of the inefficient HIV-1 Envs observed in long-term non-progressor elite controllers (LTNP-EC). On the contrary, silencing endogenous TDP-43 significantly favored the infectivity of primary Envs from VNP and RP individuals, and notably increased the infection of those from LTNP-EC. Taken together, our results indicate that TDP-43 shapes cell permissivity to HIV-1 infection, affecting viral Env fusion and infection capacities by altering the HDAC6 levels and associated tubulin-deacetylase anti-HIV-1 activity.

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Section: Introductionmentioning

confidence: 99%

Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6

Cabrera-Rodríguez

Pérez-Yanes

González-Montelongo

et al. 2022

IJMS

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“…Mutations that cause misfolding and abnormal oligomerisation of TDP-43 are associated with an expanding spectrum of neurodegenerative diseases (60). There is also increasing evidence for a role of TDP-43 in human cancers (61).…”

Section: Tdp-43 Is Recruited To Viral Mrnas Through Interaction With ...mentioning

confidence: 99%

The RBPome of influenza A virus mRNA reveals a role for TDP-43 in viral replication

Dupont

Krischuns

Gianetto

et al. 2023

Preprint

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Recent technical advances have significantly improved our understanding of the RNA-binding protein (RBP) repertoire present within eukaryotic cells, with a particular focus on the RBPs that interact with cellular polyadenylated mRNAs. However, recent studies utilising the same technologies have begun to tease apart the RBP interactome of viral mRNAs, notably SARS-CoV-2, revealing both similarities and differences between the RBP profiles of viral and cellular mRNAs. Herein, we comprehensively identified the RBPs that associate with the NP mRNA of an influenza A virus. Moreover, we provide evidence that the viral polymerase is essential for the recruitment of RPBs to viral mRNAs through direct polymerase-RBP interactions during transcription. We show that loss of TDP-43, which associates with the viral mRNAs, results in lower levels of viral mRNAs within infected cells, and a decreased yield of infectious viral particles. Overall, our results uncover an important role for TDP-43 in the influenza A virus replication cycle via a direct interaction with viral mRNAs, and point to a role of the viral polymerase in orchestrating the assembly of viral mRNPs.

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“…The TDP-43 (TAR-DNA-binding protein-43) protein is a member of the hn-RNP family, acting as a RNA and DNA binding regulator, mediating RNA metabolism and transcription regulation [114]. In IBM, pathological TDP-43 accumulates with mitochondria in degenerating muscle fibers with toxic effects [91].…”

Section: Autophagy In Ibm and Cancersmentioning

confidence: 99%

“…In IBM, pathological TDP-43 accumulates with mitochondria in degenerating muscle fibers with toxic effects [91]. These TDP-43 signaling alterations have been associated with cancers, either as a tumor promoter (upregulated in breast, lung, hepatocellular cancer, or glioblastoma), or as tumor suppressor (downregulated in cervical cancer, colon, neuroblastoma, and others) [114]. The precise molecules mediated by TDP-43 in various settings and its therapeutic consequences are yet unclear [114].…”

Section: Autophagy In Ibm and Cancersmentioning

confidence: 99%

Inclusion Body Myositis and Neoplasia: A Narrative Review

Damian

Solomon

et al. 2022

IJMS

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Inclusion body myositis (IBM) is an acquired, late-onset inflammatory myopathy, with both inflammatory and degenerative pathogenesis. Although idiopathic inflammatory myopathies may be associated with malignancies, IBM is generally not considered paraneoplastic. Many studies of malignancy in inflammatory myopathies did not include IBM patients. Indeed, IBM is often diagnosed only after around 5 years from onset, while paraneoplastic myositis is generally defined as the co-occurrence of malignancy and myopathy within 1 to 3 years of each other. Nevertheless, a significant association with large granular lymphocyte leukemia has been recently described in IBM, and there are reports of cancer-associated IBM. We review the pathogenic mechanisms supposed to be involved in IBM and outline the common mechanisms in IBM and malignancy, as well as the therapeutic perspectives. The terminally differentiated, CD8+ highly cytotoxic T cells expressing NK features are central in the pathogenesis of IBM and, paradoxically, play a role in some cancers as well. Interferon gamma plays a central role, mostly during the early stages of the disease. The secondary mitochondrial dysfunction, the autophagy and cell cycle dysregulation, and the crosstalk between metabolic and mitogenic pathways could be shared by IBM and cancer. There are intermingled subcellular mechanisms in IBM and neoplasia, and probably their co-existence is underestimated. The link between IBM and cancers deserves further interest, in order to search for efficient therapies in IBM and to improve muscle function, life quality, and survival in both diseases.

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The Regulatory Role of RNA Metabolism Regulator TDP-43 in Human Cancer

Cited by 15 publications

References 96 publications

Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6

Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6

The RBPome of influenza A virus mRNA reveals a role for TDP-43 in viral replication

Inclusion Body Myositis and Neoplasia: A Narrative Review

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