RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines

Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M.; Pritzker, Laura B.; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

which has been identified as containing an RNase cleavage site in prior studies [12, 24, 25] . The nucleotide sequence of variable region 8 was correlated by Wakeman et al. with structural features of the human 28S rRNA [28] . Based on this analysis, a double loop structure in the 3' end of the 28S rRNA contains cleavage sites identified by He et al. [24] and Houge et al. [12] which are located in the second loop of variable or expansion region 8. The estimated cleavage site in the 3'-end of the 28S rRNA from our data is also located in this loop, supporting the identification of this location as an important site vulnerable to cleavage in response to various cytotoxic stressors. In this study, fragments derived from the 18S rRNA were not detected using three different probes recognizing 18S rRNA sequences (Additional file 4), which indicates that the 18S rRNA was not cleaved within the 48 h period of exposure to docetaxel. Lack of cleavage of the 18S rRNA was reported in several studies, while others show cleavage of both the 18S and 28S rRNAs [11, 12, 17, 24, 25] . These differences in the origins of RNA disruption bands may relate to the agent/stressor inducing rRNA degradation and/or the time of incubation. For example, we have observed the loss of the 18S rRNA band on RNA electropherograms of A2780 cells incubated with taxanes, especially at the later time point of 72 h (Fig. 1a, c) .