RT Journal Article
T1 ISG20L2: an RNA nuclease regulating T cell activation
A1 Rodríguez-Galán, Ana
A1 Dosil, Sara
A1 Hrčková, Anna
A1 Fernández Messina, Lola María
A1 Feketová, Zuzana
A1 Pokorná, Julie
A1 Fernández-Delgado, Irene
A1 Camafeita, Emilio
A1 Gómez, Manuel José
A1 Ramírez-Huesca, Marta
A1 Gutiérrez-Vázquez, Cristina
A1 Sánchez-Cabo, Fátima
A1 Vázquez, Jesús
A1 Vaňáčová, Štěpánka
A1 Sánchez-Madrid, Francisco
AB 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.
PB Springer
SN 1420-682X
YR 2023
FD 2023
LK https://hdl.handle.net/20.500.14352/97250
UL https://hdl.handle.net/20.500.14352/97250
LA eng
NO Rodríguez-Galán, A., Dosil, S.G., Hrčková, A. et al. ISG20L2: an RNA nuclease regulating T cell activation. Cell. Mol. Life Sci. 80, 273 (2023). https://doi.org/10.1007/s00018-023-04925-2
NO FundingThis study was supported by grant P2022/BMD7209-INTEGRAMUNE from the Comunidad de Madrid, a grant from “La Caixa” Banking Foundation (HR17-00016) to FS-M; the Spanish Ministerio de Ciencia e Innovación (PDC2021-121719-I00 and PID-2020-120412RB-I00 to FS-M), grant from AECC, CIBER Cardiovascular (CB16/11/00272, Fondo de Investigación Sanitaria del Instituto de Salud Carlos III and co-funding by Fondo Europeo de Desarrollo Regional FEDER). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). Vaňáčová’s laboratory is supported by the Czech Science Foundation (20-19617S and 23-07372S to S.V.) and the institutional support CEITEC 2020 (LQ1601). ARG and SGD are supported by a grant from the Spanish Ministry of Universities. Funding agencies do not have intervened in the design of the studies, with no copyright over the study.
NO Centro Nacional de Investigaciones Cardiovasculares
NO Comunidad de Madrid
NO Ministerio de Economía y Competitividad (España)
NO European Commission
NO Ministerio de Ciencia, Innovación y Universidades (España)
DS Docta Complutense
RD 4 abr 2025