Transcriptional kinetics and molecular functions of long noncoding RNAs

An increasing number of long noncoding RNAs (lncRNAs) have experimentally confirmed functions, yet little is known about their transcriptional dynamics and it is challenging to determine their regulatory effects. Here, we used allele-sensitive single-cell RNA sequencing to demonstrate that, compared to messenger RNAs, lncRNAs have twice as long duration between two transcriptional bursts. Additionally, we observed increased cell-to-cell variability in lncRNA expression due to lower frequency bursting producing larger numbers of RNA molecules. Exploiting heterogeneity in asynchronously growing cells, we identified and experimentally validated lncRNAs with cell state-specific functions involved in cell cycle progression and apoptosis. Finally, we identified cis-functioning lncRNAs and showed that knockdown of these lncRNAs modulated the nearby protein-coding gene's transcriptional burst frequency or size. In summary, we identified distinct transcriptional regulation of lncRNAs and demonstrated a role for lncRNAs in the regulation of mRNA transcriptional bursting. Allele-sensitive single-cell RNA sequencing analysis of long noncoding RNA (lncRNA) transcriptional kinetics shows that their lower expression compared to mRNA is due to lower burst frequencies and highlights cell-state-specific functions for several lncRNAs.

Automated summary

This study utilized allele-sensitive single-cell RNA sequencing to investigate the transcriptional dynamics of long noncoding RNAs (lncRNAs). The results showed that lncRNAs have a longer duration between two transcriptional bursts compared to messenger RNAs. The study also observed increased cell-to-cell variability in lncRNA expression, which is attributed to lower burst frequencies producing larger quantities of RNA molecules. Furthermore, the study identified lncRNAs with cell state-specific functions involved in cell cycle progression and apoptosis and demonstrated their regulatory effects on nearby protein-coding genes' transcriptional bursting.