U2AF - Hypoxia-induced fas alternative splicing regulator

Vilys, Laurynas; Pečiulienė, Inga; Jakubauskienė, Eglė; Zinkevičiūtė, Rūta; Makino, Yuichi; Kanopka, Arvydas

doi:10.1016/j.yexcr.2020.112444

Cited by 10 publications

(7 citation statements)

References 50 publications

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“…At the start of the 2000s, Wei and colleagues showed that overexpression of polypyrimidine tract-binding protein (PTBP1), one of the key regulators of mRNA splicing (reviewed in [ 145 , 146 , 147 ]), induced Tau 6 exon exclusion in COS cells, while overexpression of U2AF [ 148 ] promoted exon 6 retention in the mature mRNA [ 87 ]. Strikingly, the authors report that simultaneous overexpression of both proteins yielded the same outcome as overexpression of PTBP1 alone, suggesting that the two RBPs could compete for the same binding sites on the target mRNA [ 87 ].…”

Section: Alternative Splicing Regulation Of Tau Exonsmentioning

confidence: 99%

Tau Isoforms: Gaining Insight into MAPT Alternative Splicing

Corsi

Bombieri

Valenti

2022

IJMS

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Tau microtubule-associated proteins, encoded by the MAPT gene, are mainly expressed in neurons participating in axonal transport and synaptic plasticity. Six major isoforms differentially expressed during cell development and differentiation are translated by alternative splicing of MAPT transcripts. Alterations in the expression of human Tau isoforms and their aggregation have been linked to several neurodegenerative diseases called tauopathies, including Alzheimer’s disease, progressive supranuclear palsy, Pick’s disease, and frontotemporal dementia with parkinsonism linked to chromosome 17. Great efforts have been dedicated in recent years to shed light on the complex regulatory mechanism of Tau splicing, with a perspective to developing new RNA-based therapies. This review summarizes the most recent contributions to the knowledge of Tau isoform expression and experimental models, highlighting the role of cis-elements and ribonucleoproteins that regulate the alternative splicing of Tau exons.

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Section: Alternative Splicing Regulation Of Tau Exonsmentioning

confidence: 99%

Tau Isoforms: Gaining Insight into MAPT Alternative Splicing

Corsi

Bombieri

Valenti

2022

IJMS

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“…Overexpression of sCD95 has been detected in a wide range of cancers ( 75 , 76 ). Recently, hypoxic microenvironments were found to modulate CD95 splicing and promote the production of anti-apoptotic sCD95 mRNA ( 77 ), possibly due to reduced interactions of the splicing factor U2AF-RNA in hypoxic cells ( 78 ).…”

Section: Disruption Of Cd95-mediated Apoptotic Signaling In Gbmsmentioning

confidence: 99%

The dual role of the CD95 and CD95L signaling pathway in glioblastoma

et al. 2022

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Binding of CD95, a cell surface death receptor, to its homologous ligand CD95L, transduces a cascade of downstream signals leading to apoptosis crucial for immune homeostasis and immune surveillance. Although CD95 and CD95L binding classically induces programmed cell death, most tumor cells show resistance to CD95L-induced apoptosis. In some cancers, such as glioblastoma, CD95-CD95L binding can exhibit paradoxical functions that promote tumor growth by inducing inflammation, regulating immune cell homeostasis, and/or promoting cell survival, proliferation, migration, and maintenance of the stemness of cancer cells. In this review, potential mechanisms such as the expression of apoptotic inhibitor proteins, decreased activity of downstream elements, production of nonapoptotic soluble CD95L, and non-apoptotic signals that replace apoptotic signals in cancer cells are summarized. CD95L is also expressed by other types of cells, such as endothelial cells, polymorphonuclear myeloid-derived suppressor cells, cancer-associated fibroblasts, and tumor-associated microglia, and macrophages, which are educated by the tumor microenvironment and can induce apoptosis of tumor-infiltrating lymphocytes, which recognize and kill cancer cells. The dual role of the CD95-CD95L system makes targeted therapy strategies against CD95 or CD95L in glioblastoma difficult and controversial. In this review, we also discuss the current status and perspective of clinical trials on glioblastoma based on the CD95-CD95L signaling pathway.

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“…A recent report revealed that splicing factor U2AF, due to an increase in phosphorylation level of both subunits, which influence the factor's interaction with RNA, plays an important role in hypoxia-dependent splicing regulation of Fas pre-mRNA [78]. As neurodegenerative diseases, such as AD and PD, are associated with hypoxic conditions, it is still an open question whether splicing factor U2AF is involved in splicing regulation of neurodegeneration related genes under hypoxic conditions in brain cells.…”

Section: Hypoxia Splicing and Neurodegenerationmentioning

confidence: 99%

Alternative Splicing and Hypoxia Puzzle in Alzheimer’s and Parkinson’s Diseases

Jakubauskienė

Kanopka

2021

Genes

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Alternative pre-mRNA splicing plays a very important role in expanding protein diversity as it generates numerous transcripts from a single protein-coding gene. Therefore, alterations lead this process to neurological human disorders, including Alzheimer’s and Parkinson’s diseases. Moreover, accumulating evidence indicates that the splicing machinery highly contributes to the cells’ ability to adapt to different altered cellular microenvironments, such as hypoxia. Hypoxia is known to have an effect on the expression of proteins involved in a multiple of biological processes, such as erythropoiesis, angiogenesis, and neurogenesis, and is one of the important risk factors in neuropathogenesis. In this review, we discuss the current knowledge of alternatively spliced genes, which, as it is reported, are associated with Alzheimer’s and Parkinson’s diseases. Additionally, we highlight the possible influence of cellular hypoxic microenvironment for the formation of mRNA isoforms contributing to the development of these neurodegenerative diseases.

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U2AF - Hypoxia-induced fas alternative splicing regulator

Cited by 10 publications

References 50 publications

Tau Isoforms: Gaining Insight into MAPT Alternative Splicing

Tau Isoforms: Gaining Insight into MAPT Alternative Splicing

The dual role of the CD95 and CD95L signaling pathway in glioblastoma

Alternative Splicing and Hypoxia Puzzle in Alzheimer’s and Parkinson’s Diseases

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