Transcriptional kinetics and molecular functions of long non-coding RNAs

An increasing number of long non-coding RNAs (lncRNAs) have confirmed important functions, yet little is known about their transcriptional dynamics and it remains challenging to determine their regulatory functions. Here, allele-sensitive single-cell RNA-seq was used to demonstrate that lncRNAs have lower burst frequencies compared to mRNAs. We observed an increased cell-to-cell variability in lncRNA expression that was due to more sporadic bursting (lower frequency) with larger numbers of RNA molecules being produced. 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 knockdown of these lncRNAs modulated either transcriptional burst frequency or size of the nearby protein-coding gene. Collectively, we identify distinct transcriptional regulation of lncRNAs and we demonstrate a role for lncRNAs in the regulation of transcriptional bursting of mRNAs.