Dicer-microRNA-Myc circuit promotes transcription of hundreds of long noncoding RNAs

Long noncoding RNAs (IncRNAs) are important regulators of cell fate, yet little is known about mechanisms controlling IncRNA expression. Here we show that transcription is quantitatively different for IncRNAs and mRNAs-as revealed by deficiency of Dicer (Dcr), a key RNase that generates microRNAs (miRNAs). Dcr loss in mouse embryonic stem cells led unexpectedly to decreased levels of hundreds of IncRNAs. The canonical Dgcr8-Dcr-miRNA pathway is required for robust IncRNA transcriptional initiation and elongation. Computational and genetic epistasis analyses demonstrated that Dcr activation of the oncogenic transcription factor cMyc is partly responsible for IncRNA expression. A quantitative metric of mRNA-IncRNA decoupling revealed that Dcr and cMyc differentially regulate IncRNAs versus mRNAs in diverse cell types and in vivo. Thus, numerous IncRNAs may be modulated as a class in development and disease, notably where Dcr and cMyc act.