Dataset Information


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

ABSTRACT: Long noncoding RNAs (lncRNAs) are important regulators of cell fate, and their mis-expression has been implicated in many diseases. While distinct polymerases generate messenger vs. noncoding ribosomal or tRNAs3, little is known about distinct mechanisms controlling lncRNA expression. Here we show that transcription of lncRNAs is quantitatively different from that of messenger RNAs (mRNAs)--as revealed by deficiency of Dicer (Dcr), a key ribonuclease that generates microRNAs (miRNAs). Loss of Dcr in mouse embryonic stem cells (mESCs) led surprisingly to decreased level of the majority of lncRNAs. The canonical Dgcr8-Dcr-miRNA pathway is required for robust lncRNA expression, at the level of transcriptional initiation and elongation of lncRNA genes rather than at the level of their stability. cMyc, an oncogenic transcription factor, whose expression is indirectly regulated by Dcr-miRNA in mESCs, is partly responsible for lncRNA transcription. Loss of cMyc led to a more dramatic decrease of lncRNAs than mRNAs, and cMyc overexpression rescues lncRNA expression in Dcr KO cells. A quantitative metric of “mRNA-lncRNA decoupling” revealed that Dcr and cMyc differentially regulate lncRNAs vs. mRNAs in diverse cell types and in vivo, as evidenced by hundreds of microarray experiments. Thus, Dcr and cMyc may allow numerous lncRNAs to be activated or deactivated as a class, implicating lncRNAs to potential regulatory roles in development and disease states where Dcr and cMyc have been associated with. RNA was sequenced from WT and Dcr KO mESCs and the expression of lncRNAs and mRNAs are compared between WT and Dcr KO mESCs.

ORGANISM(S): Mus musculus  

SUBMITTER: Dan Webster   Paul Khavari  Howard Chang  Grace X Zheng  Kun Qu  Brian Do 

PROVIDER: E-GEOD-55338 | ArrayExpress | 2014-06-15



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