Figure 8.

Cartoon depicting the general response of cultured cells to commonly used oxidative stressors such as As[III] or H₂O₂ during two major phases of the experimental manipulation. During the acute phase of the stress response, which, depending on the chemical stressor lasts from one to several hours (red arrow below dashed time line), cells respond with SG formation and an increase in tRNA fragmentation (lower graphs). Upon removal of the respective stressor and culture in recovery medium (green arrow), cells either survive or die, depending on the strength of the acute insult. While SG are dissolved within a few hours after stress removal, a large proportion of cells in recovery medium initiate pathways, which ultimately lead to loss of membrane integrity, increasing RNA degradation and cell death, which is concomitant with the appearance of stable ex-tsRNAs in the cell culture medium. During both phases, tsRNAs can be detected in cells using northern blotting. Since the peak of tsRNA signals is detectable during the acute phase, these small RNAs are likely exerting specific functions within cells related to acute stress responses. In contrast, the low level of tsRNAs that are produced after stress removal including the accumulation of ex-tsRNAs in cell culture media indicate that cell death-related processes contribute to the production of these small RNAs, which have either no biological function or play undefined roles as signaling molecules.