Global stabilization of the transcriptome in mitotic cells

In the presence of cell division errors, mammalian cells can pause in mitosis for tens of hours with little to no transcription, while still requiring continued translation for viability. These unique aspects of mitosis require substantial adaptations to gene expression. During interphase, homeostatic control of mRNA levels involves a constant balance of transcription and degradation, with a median mRNA half-life of ~2-4 h. If such short half-lives persisted in mitosis, cells would be expected to rapidly deplete their transcriptome without new transcription. Here, we report that the transcriptome is globally stabilized during prolonged mitotic delays. Median mRNA half-lives are increased >4-fold during mitotic arrest compared to interphase, buffering mRNA levels in the absence of new synthesis. Moreover, poly(A) tail-length profiles change during mitotic arrest, strongly suggesting a partial mitotic repression of deadenylation. In contrast, siRNA-directed mRNA degradation machinery remains active. We further show that mitotic mRNA stabilization depends on PABPC1&4. Depletion of PABPC1&4 during mitotic arrest reduces mRNA stability and disrupts the cells' ability to maintain arrest, highlighting the critical physiological role of mitotic transcriptome buffering.