Long noncoding RNA-dependent control of transcriptional bursting

Genes are transcribed in short periods of activity, called bursts. The duration of each burst is dynamically controlled by the levels of promoter- and enhancer-produced RNAs through a negative feedback mechanism. However, the contribution of neighboring transcripts to the regulation of bursting is not known. Here, we show that chromatin-associated long noncoding RNAs (lncRNAs) are local fine-tuners of transcriptional bursting. We found that constitutive production of the lncRNA Pvt1 raises the baseline of RNA concentration in the locus of the Myc proto-oncogene and acts locally in a dose-dependent manner to decrease the duration of Myc bursting. Premature termination of Pvt1 led to higher Myc expression and oncogenic activities, including increased cellular proliferation and advanced tumor development in an autochthonous model of lung cancer. These findings point to a widespread role for lncRNAs in fine-tuning gene expression through local control of transcriptional bursting.