UPREGULATION OF IMMUNOSTIMULATORY NON-CODING RNAS DURING THE CELLULAR RESPONSE TO STRESS

GIMENEZ, MACARENA; BOCCACCIO, GRACIELA L; LA SPINA, PABLO; CONTRERAS, NATALIA; FERNÁNDEZ ALVAREZ, ANA JULIA

Virtual

Congreso; Congreso Conjunto SAIB-SAMIGE 2020; 2020

SAIB

The stress response and innate immunity are linked through complex, ill-defined pathways. A conserved arm of the stress response is a transient and massive translational silencing. Polysome-free non-translating mRNAs accumulate in specific cytosolic bodies termed stress granules (SGs). SGs serve as a platform for the activation of RIG I, a major intracellular pattern recognition receptor (Perez-Pepe et al 2018; Thomas et al; 2011). RIG I is activated by viral and endogenous RNAs, including non-coding Y RNA and Vault RNAs. PKR -another key antiviral factor present in SGs- is controlled by viral and endogenous ncRNAs as well. Whether immunostimulatory ncRNAs respond to stress is unknown. Here we analyzed the expression of selected ncRNAs upon acute oxidative stress in cultured mammalian cell lines. Non-radioactive northern blot analysis and quantitative RT-PCR indicated that AluRNA, Vault 1-1 RNA and Vault 1-2 RNA levels increases after exposure to arsenite. Vault RNAs upregulation was confirmed by fluorescent in situ hybridization. Vault 1-1 gradually increased accompanying HSP70 mRNA induction. Overexpression of Vault RNAs in transient-transfection experiments did not affect HSP70 mRNA expression, suggesting that Vault RNA upregulation is a consequence rather than a trigger of the stress response. Current studies are aimed to investigate the contribution of these non-coding RNAs to RIG-1 and PKR activation.