ISG20L2: an RNA nuclease regulating T cell activation
ISG20L2, a 3′ to 5′ exoribonuclease previously associated with ribosome biogenesis, is identified here in activated T cells as an enzyme with a preferential affinity for uridylated miRNA substrates. This enzyme is upregulated in T lymphocytes upon TCR and IFN type I stimulation and appears to be inv...
| Autores: | , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/97250 |
| Acceso en línea: | https://hdl.handle.net/20.500.14352/97250 |
| Access Level: | acceso abierto |
| Palabra clave: | 576 577.2 612.017 ISG20L2 Exonuclease T cell Immunoregulatory Biología celular (Biología) Biología molecular (Biología) Inmunología 2407 Biología Celular 2415 Biología Molecular 2412 Inmunología |
| Sumario: | ISG20L2, a 3′ to 5′ exoribonuclease previously associated with ribosome biogenesis, is identified here in activated T cells as an enzyme with a preferential affinity for uridylated miRNA substrates. This enzyme is upregulated in T lymphocytes upon TCR and IFN type I stimulation and appears to be involved in regulating T cell function. ISG20L2 silencing leads to an increased basal expression of CD69 and induces greater IL2 secretion. However, ISG20L2 absence impairs CD25 upregulation, CD3 synaptic accumulation and MTOC translocation towards the antigen-presenting cell during immune synapsis. Remarkably, ISG20L2 controls the expression of immunoregulatory molecules, such as AHR, NKG2D, CTLA-4, CD137, TIM-3, PD-L1 or PD-1, which show increased levels in ISG20L2 knockout T cells. The dysregulation observed in these key molecules for T cell responses support a role for this exonuclease as a novel RNA-based regulator of T cell function. |
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