Identification of importin alpha1 as a novel constituent of RNA stress granules

Importin alpha is a nuclear transport receptor well established for its ability to mediate importin beta-mediated nuclear import of proteins that possess classical nuclear localization signal (cNLS). Previously, we reported that importin alpha rapidly accumulates to the nucleus in response to H2O2-induced oxidative stress, which implies a role for this protein in stress response. In this study, we show that importin alpha1 (also known as KPNA2 or Rch1), a major subtype of the importin alpha family, localizes to RNA stress granules (SGs), large cytoplasmic bodies that are thought to function as RNA triage sites during stress response. The recruitment of importin alpha1 to SGs was compatible with its nuclear accumulation during heat shock. Depletion of endogenous importin alpha1 using siRNA showed that importin alpha1 regulates the dynamics of SG assembly, and that it promotes cell survival in arsenite-treated cells. These data revealed, for the first time, the involvement of importin alpha in the assembly of RNA granules and its pro-survival role during stress response.