Differential nuclear import regulates nuclear RNA inheritance following mitosis

Mitosis results in a dramatic reorganization of chromatin structure to promote chromosome compaction and segregation to daughter cells. Consequently, mitotic entry is accompanied by transcriptional silencing and removal of most chromatin-bound RNA from chromosomes. As cells exit mitosis, chromatin rapidly decondenses and transcription restarts as waves of differential gene expression. However, little is known about the fate of chromatin-bound RNAs following cell division. Here we explored whether nuclear RNA from the previous cell cycle is present in G1 nuclei following mitosis. We found that half of all nuclear RNA is inherited in a transcription-independent manner following mitosis. Interestingly, the snRNA U2 is efficiently inherited by G1 nuclei, while the lncRNAs NEAT1 and MALAT1 show no inheritance following mitosis. We found that the nuclear protein SAF-A, which is hypothesized to tether RNA to DNA, did not play a prominent role in nuclear RNA inheritance, indicating that the mechanism for RNA inheritance may not involve RNA chaperones that have chromatin-binding activity. Instead, we observe that the timing of RNA inheritance indicates that a select group of nuclear RNAs are reimported into the nucleus after the nuclear envelope has reassembled. Our work demonstrates that there is a fraction of nuclear RNA from the previous cell cycle that is reimported following mitosis and suggests that mitosis may serve as a time to reset the interaction of lncRNAs with chromatin.