SLFN2 protection of tRNAs from stress-induced cleavage is essential for T cell-mediated immunity.
Science
; 372(6543)2021 05 14.
Article
em En
| MEDLINE
| ID: mdl-33986151
ABSTRACT
Reactive oxygen species (ROS) increase in activated T cells because of metabolic activity induced to support T cell proliferation and differentiation. We show that these ROS trigger an oxidative stress response that leads to translation repression. This response is countered by Schlafen 2 (SLFN2), which directly binds transfer RNAs (tRNAs) to protect them from cleavage by the ribonuclease angiogenin. T cell-specific SLFN2 deficiency results in the accumulation of tRNA fragments, which inhibit translation and promote stress-granule formation. Interleukin-2 receptor ß (IL-2Rß) and IL-2Rγ fail to be translationally up-regulated after T cell receptor stimulation, rendering SLFN2-deficient T cells insensitive to interleukin-2's mitogenic effects. SLFN2 confers resistance against the ROS-mediated translation-inhibitory effects of oxidative stress normally induced by T cell activation, permitting the robust protein synthesis necessary for T cell expansion and immunity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA de Transferência
/
Linfócitos T
/
Estresse Oxidativo
/
Proteínas de Ciclo Celular
/
Imunidade Celular
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article